Process for the preparation of 3, 3-dimethylbutanal

ABSTRACT

3,3-Dimethylbutanal is prepared from 3,3-dimethylbutanol. Intermediate 3,3-dimethylbutanol is obtained by reacting ethylene, isopropylene and a mineral acid to produce a 3,3-dimethylbutyl ester which is hydrolyzed to the alcohol. The hydrolysis step is effectively carried out by reactive distillation. Alternatively, 3,3-dimethylbutanal is prepared from 3,3-dimethylbutanol obtained by reduction of the corresponding carboxylic acid or 1,2-epoxy-3,3-dimethylbutane, or by hydrolysis of 1-halo-3,3-dimethylbutane. Fixed bed gas phase and stirred tank liquid phase processes are provided for converting 3,3-dimethylbutanol to 3,3-dimethylbutanal by catalytic dehydrogenation.

BACKGROUND OF THE INVENTION

[0001] This invention relates to the preparation of 3,3-dimethylbutanal, and more particularly to improved processes for preparing3,3-dimethylbutanal and precursors therefor.

[0002] Nofre et al. U.S. Pat. No. 5,480,668 describes artificialsweetening agents comprising N-substituted derivatives of aspartame. Apreferred example as described by Nofre isN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester. Asthe reference further describes, this product may be produced byreaction of 3,3-dimethylbutyraldehyde (3,3-dimethylbutanal) withaspartame and a reducing agent such as sodium cyanoborohydride in asolvent medium such as methanol.

[0003] Nofre U.S. Pat. No. 5,510,508 and Prakash U.S. Pat. No. 5,728,862describe preparation ofN-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine, 1-methyl esterby a reductive alkylation reaction comprising catalytic hydrogenation ofthe Schiff's based produced by condensation of 3,3-dimethylbutanal andaspartame.

[0004] To facilitate the manufacture ofN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester,there has been a need in the art for an improved and economical methodfor preparation of the 3,3-dimethylbutanal intermediate. Currently,3,3-dimethylbutanal is available on the market only in limitedquantities at prices that are very expensive. Previously availablemanufacturing processes have generally failed to provide satisfactoryyields, or to produce an aldehyde intermediate of adequate purity,substantially free of by-products, such as t-butylacetic acid. Recently,improved methods have been developed, but a need has remained for a moresatisfactory process for the commercial manufacture of3,3-dimethylbutanal.

[0005] Prakash et al. U.S. Pat. No. 5,856,584 describes a process forthe preparation of 3,3-dimethylbutanal by oxidation of3,3-dimethylbutanol. Oxidizing components used in the process include anoxidizing metal oxide or 2,2,6,6-tetramethyl-1-piperidinyloxy, freeradical, and an oxidizing agent such as sodium hypochlorite. Oxidationby a metal oxide may effected by contacting 3,3-dimethylbutanol in avapor phase comprising an inert carrier gas with an oxidizing metaloxide. Oxidation by 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical,and sodium hypochlorite may be conducted in a solvent system.

[0006] Slaugh U.S. Pat. No. 4,891,446 describes a process for catalyticdehydrogenation of saturated primary alcohols having a carbon numberranging from 5 to 20, preferably 7 to 18. The alcohol is passed over afixed bed of brass particles in a vertical column or horizontal tubularreactor. Although hydrogen is a product of the reaction, additionalhydrogen is introduced into the reactor in order to obtain good catalystlife or stability. Specific working examples are given fordehydrogenation of C₉, C₁₃, and C₁₅ alcohols.

[0007] Gulkova et al. “Dehydrogenation of Substituted Alcohols toAldehydes on Zinc Oxide-Chromium Oxide Catalysts,” Collect. Czech. Chem.Commun., Vol. 57, pp. 2215-2226 (1992) reports the exploration ofsixteen primary alcohols for the possibility of obtaining thecorresponding aldehydes by dehydrogenation on solid catalysts. Among thesubstrates tested was 3,3-dimethyl-butanol. The reference reportscertain rate constant information for the dehydrogenation of a3,3-dimethylbutanol substrate, but does not include description of theparticular conditions under which this substrate was converted to3,3-dimethylbutanal.

[0008] Banthorpe et al., “Mechanism of Elimination Reactions. Part XX.The Inessentiality of Steric Strain in Bimolecular Olefin Elimination,”J. C. S., 1960, pp. 4084-4087 describes the dehydrogenation of3,3-dimethylbutanol to 3,3-dimethylbutanal in which 3,3-dimethylbutanolwas boiled into a vertical tube containing pumice supported copperchromite catalyst and surmounted by a reflux condenser. The catalystbecame reduced after 40 minutes reaction and was regenerated by exposureto an air stream at 320° C. for 2 hours.

[0009] Where 3,3-dimethylbutanal is derived from 3,3-dimethylbutanol,the provision of a satisfactory commercial method for the preparation ofthe aldehyde also requires the selection and/or development of aneconomically effective method for the preparation of the alcohol.

[0010] Hoffman et al. U.S. Pat. No. 3,754,052 describes reaction ofisobutylene, ethylene and sulfuric acid in the presence of isobutane toproduce the sulfate ester of 3,3-dimethylbutanol in isobutane. Unreactedethylene is removed and the sulfate ester is alkylated with isobutane at≧25° C. to produce 2,3-dimethylbutane.

[0011] Wiese U.S. Pat. No. 2,660,602 describes a process for thepreparation of branched primary sulfate esters by reaction of ethylene,an olefin co-reactant and sulfuric acid, particularly including thepreparation of 3,3-dimethylbutyl hydrogen sulfate where the olefinco-reactant is isobutylene. The reaction is carried out bysimultaneously contacting strong sulfuric acid with ethylene and theco-reactant, preferably in the cold. A high ethylene to co-reactantratio is maintained. A hydrocarbon diluent is preferably present in thereaction zone, particularly when employing low molecular weightco-reactants, i.e., less than C₁₂. The reference disclosed hydrolysis of3,3-dimethylbutyl monohydrogen sulfate ester to 3,3-dimethylbutanol, andfurther suggests the preparation of the acetate of the alcohol, which issaid to be useful as a lacquer solvent. Wiese et al. also suggestpreparation of di-octyl phthalate ester plasticizers by esterificationof phthalic anhydride with branched chain alcohol.

[0012] Reactions have been described in which carboxylic acids andesters are reduced to alcohol by reaction with strong reducing agentscommonly lithium aluminum hydride. Such reactions must be handled withcaution due to the high reactivity of the reducing agents. Journal ofOrganic Chemistry, Vol. 46 (1981), pp. 2579-2581 discloses thatcarboxylic acid amides can be reduced to the corresponding amines by acombination of sodium borohydride and methane sulfonic acid anddimethylsulfoxide (DMSO). The same paper discloses that acetic acid andphenyl acetic acid can be reduced to corresponding alcohols undersimilar conditions. However, the paper contains no suggestion of thereduction of other acids to the corresponding alcohols. Sodiumborohydride is a widely used reducing agent and relatively safe to workwith but has not been considered generally suitable for reducing thecarboxylate group due to its mild reducing capacity.

[0013]Journal of the American Chemical Society, Vol. 73 (1951), p. 555discloses hydrolysis of 1-chloro-3,3-dimethylbutane with potassiumcarbonate in a closed system to produce 3,3-dimethylbutanol in 65%yield. Since carbon dioxide is generated in the reaction, the procedurerequires operation at high pressure to avoid stripping out the aqueousphase.

SUMMARY OF THE INVENTION

[0014] Among the several objects of the present invention, therefore,may be noted the provision of a process for the manufacture of3,3-dimethylbutanal; the provision of such a process which uses readilyavailable and inexpensive raw materials; the provision of a processwhich produces intermediates for 3,3-dimethylbutanal; the provision ofprocesses which provide high yields in the preparation of3,3-dimethylbutanal and/or intermediates therefor; the provision of aprocess for the preparation of 3,3-dimethylbutanol; the provision of aprocess for preparation of 3,3-dimethylbutanol and use thereof as asubstrate for conversion to 3,3-dimethylbutanal; the provision of aprocess for producing 3,3-dimethylbutanol and converting it to3,3-dimethylbutanal without substantial refining of the3,3-dimethylbutanol; the provision of a process for the preparation of3,3-dimethylbutanal which does not require generation of halideby-products or impurities; the provision of processes for themanufacture of 3,3-dimethylbutanol and 3,3-dimethylbutanal which can beimplemented with acceptable capital investment and operating cost; andthe provision of a process for preparation of 3,3-dimethylbutanal anduse thereof for the preparation ofN-[N-(3,3-dimethylbutyl)-L-αaspartyl]-L-phenylalanine 1-methyl ester(sometimes hereinafter referred to as “neotame”).

[0015] Briefly, therefore, the present invention is directed to aprocess for the preparation of 3,3-dimethylbutanal. An ester of3,3-dimethylbutanol is prepared by reacting isobutylene, ethylene, andthe mineral acid. The ester is hydrolyzed to produce3,3-dimethylbutanol; and the alcohol is converted to3,3-dimethylbutanal.

[0016] The invention is further directed to a process for thepreparation of 3,3-dimethylbutanal comprising contacting3,3-dimethylbutanol with a catalyst for the dehydrogenation of analcohol to a corresponding aldehyde at a turnover ratio of at least 5moles dimethylbutanal per mole catalyst active phase prior to anyinterruption of the reaction for regeneration of catalyst.

[0017] The invention further comprises a process for preparation of3,3-dimethylbutanol in which a hydrolysis feed mixture comprising a3,3-dimethylbutyl ester and a mineral acid is heated in the presence ofwater, thereby hydrolyzing the ester and producing a hydrolysis reactionmixture comprising 3,3-dimethylbutanol. The 3,3-dimethylbutanol formedin the hydrolysis is distilled from the hydrolysis reaction mixture.

[0018] The invention is further directed to a process for thepreparation of 3,3-dimethylbutanal in which a gas phase comprising3,3-dimethylbutanol and an inert gas is contacted with a dehydrogenationcatalyst to produce a dehydrogenation reaction product gas containing3,3-dimethylbutanal at a turnover ratio of at least 5 molesdimethylbutanal per mole catalyst active phase prior to any interruptionof the reaction for regeneration of catalyst. 3,3-Dimethylbutanal isrecovered from the dehydrogenation reaction mixture.

[0019] The invention is further directed to a process for thepreparation of 3,3-dimethylbutanal in which a slurry comprising aparticulate dehydrogenation catalyst and 3,3-dimethylbutanol isprepared, and 3,3-dimethylbutanol is converted to 3,3-dimethylbutanal bycatalytic dehydrogenation in the slurry. A dehydrogenation reactionproduct slurry comprising the catalyst and 3,3-dimethyl butanal isproduced. 3,3-Dimethylbutanal is recovered from the dehydrogenationreaction product slurry.

[0020] The invention further comprises a process for the preparation of3,3-dimethylbutanal in which 3,3-dimethyl butanoic acid or an esterthereof is contacted with the reducing agent thereby producing3,3-dimethylbutanol. 3,3-Dimethylbutanol is converted to 3,3-dimethylbutanal.

[0021] The invention is also directed to a process for the preparationof 3,3-dimethylbutanal in which a substrate selected from the groupconsisting of 1-chloro-3,3-dimethylbutane and 1-bromo-3,3-dimethylbutaneis hydrolyzed to produce 3,3-dimethyl butanol. 3,3-Dimethylbutanol isconverted to 3,3-dimethylbutanal.

[0022] The invention is further directed to a process for preparing3,3-dimethylbutanal in which 3,3-dimethylbutanal is prepared byhydrolysis of 1-halo-3,3-dimethylbutane or 1-acyloxy-3,3-dimethylbutanein the presence of a base; and the 3,3-dimethylbutanol is converted to3,3-dimethylbutanal.

[0023] The invention is also directed to a process for preparing3,3-dimethylbutanol in which 1,2-epoxy-3,3-dimethylbutane oxide isreduced to 3,3-dimethylbutanol and 3,3-dimethylbutanol is converted to3,3-dimethylbutanal.

[0024] The invention is also directed to a process for preparation of3,3-dimethylbutanal in which a t-butyl organometallic compound isreacted with ethylene oxide to form 3,3-dimethylbutanol and3,3-dimethylbutanol is converted to 3,3-dimethylbutanal.

[0025] The invention is further directed to a process for thepreparation of 3,3-dimethylbutanal in which 3,3-dimethylbutanol iscontacted with a catalyst for the dehydrogenation of an alcohol to acorresponding aldehyde the catalyst is substantially non-toxic tohumans.

[0026] Other objects and features will be in part apparent and in partpointed out hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027]FIG. 1 plots total 3,3-dimethylbutanol yield and yield on sulfuricacid, ethylene and isobutylene as a function of reactant addition timeduring the alkylation/esterification reaction for the combinedalkylation/esterification and hydrolysis reactions described in Example2 as conducted under the conditions designated in the graph;

[0028]FIG. 2 plots 3,3-dimethylbutanol yield based on isobutylene,ethylene (reacted), ethylene (feed), and sulfuric acid as a function ofethylene pressure during the alkylation/esterification reaction for thecombined alkylation/esterification and hydrolysis reactions of Example 2under the otherwise fixed conditions designated on the plot;

[0029]FIG. 3 sets forth plots of cumulative ethylene uptake as afunction of time for varying ethylene pressures during thealkylation/esterification reaction for the combinedalkylation/esterification and hydrolysis reactions of Example 2 asconducted under otherwise fixed conditions as designated on the diagram;

[0030]FIG. 4 is a plot of selectivity as a function of time during thefixed bed catalytic dehydrogenation of 3,3-dimethylbutanol to3,3-dimethylbutanal described in Example 6;

[0031]FIG. 5 plots 3,3-dimethylbutanal content, 3,3-dimethylbutanolcontent, conversion and selectivity in the catalytic dehydrogenation of3,3-dimethylbutanol to 3,3-dimethylbutanal as a function of time duringthe 48 hour dehydrogenation run of Example 7;

[0032]FIG. 6 plots the impurity content in the dehydrogenation reactiongas as a function of time during the 48 hour dehydrogenation run ofExample 7;

[0033]FIG. 7 is a block flow diagram of the overall process of theinvention for the preparation of 3,3-dimethylbutanal;

[0034]FIG. 8 is a process equipment diagram and flow sheet for anembodiment of the overall process of the invention for the continuouspreparation 3,3-dimethylbutanol;

[0035]FIG. 9 is a process equipment diagram and flow sheet for anembodiment of the catalytic dehydrogenation of 3,3-dimethylbutanol to3,3-dimethylbutanal; and

[0036]FIG. 10 is a process equipment diagram and flow sheet for analternative embodiment of the catalytic dehydrogenation process.

[0037] Corresponding reference characters indicate corresponding partsthroughout the drawings.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038] In accordance with the present invention, novel and advantageousprocesses have been developed for the preparation of3,3-dimethylbutanol, 3,3-dimethylbutanal andN-[N-(3,3-dimethylbutyl)-1-α-aspartyl]-L-phenylalanine 1-methyl ester(neotame).

[0039] In an alkylation and esterification reaction comprising theinitial step in the preparation of 3,3-dimethylbutanol, isobutylene,ethylene and a mineral acid are reacted to produce a mixture comprisingan ester of 3,3-dimethylbutanol and the mineral acid. For example, usingsulfuric acid as the mineral acid, monoesters and diesters are typicallyproduced according the following reaction:

[0040] The 3,3-dimethylbutyl monoesters and diesters are hydrolyzed toproduce 3,3-dimethylbutanol, which is preferably recovered from thehydrolysis reaction mixture by distillation:

[0041] 3,3-Dimethylbutanol is converted to 3,3-dimethylbutanal bycatalytic dehydrogenation:

[0042] Optionally, in certain embodiments of the invention,3,3-dimethylbutanol can be converted to 3,3-dimethylbutanal in thepresence of molecular oxygen and a catalyst for oxidativedehydrogenation of an aldehyde:

[0043] 3,3-Dimethylbutanal is useful as a raw material for thepreparation of N-(3,3-dimethylbutyl)aspartame, a novel sweetener asdescribed in U.S. Pat. No. 5,480,668. Preparation of neotame may proceedby reductive alkylation of aspartame comprising formation of theSchiff's base:

[0044] and catalytic addition of hydrogen across the —C═N— double bondto yield:

[0045] In the preparation of 3,3-dimethylbutanol esters, isobutylene isintroduced into a mineral acid medium under an ethylene atmosphere. Avariety of mineral acids can be used to catalyze the reaction and supplythe anion from which the esters are formed. A relatively strong acid isrequired, e.g., an acid exhibiting pK_(a) no greater than about 0. Amongthe acids which can be used in the reaction are sulfuric, oleum,sulfurous, and trifluoromethane sulfonic, and nitric. Alternatively, acation-exchange resin, e.g., a sulfonated resin such as that sold underthe trade designation “Nafion” by E. I. duPont de Nemours & Co can beused to catalyze the reaction. Sulfuric acid is preferred.

[0046] In conducting the alkylation and esterification reaction,isobutylene and ethylene are brought simultaneously into contact withthe mineral acid within an alkylation/esterification reaction zone. Inthe reaction zone, the olefin reactants are introduced into a condensedphase reaction medium which comprises the mineral acid, and normallyfurther comprises a nonpolar organic solvent. Thus, the reaction systemis typically three phase, including the acid phase, the solvent phaseand a gas phase comprising primarily ethylene. Preferably, the reactantsare contacted under relatively vigorous agitation to promote transfer ofethylene from the gas phase to the solvent phase, establish substantialinterfacial contact between the solvent and acid phases, promotetransfer of the olefinic reactants to the interface between the liquidphases, and promote transfer of product esters from the interface intothe acid phase. While the process of the invention does not depend onany particular theory, it is believed that, in the presence of acid, at-butyl cation is formed from the isobutylene and reacts with theethylene and mineral acid to produce the monoester, e.g., in the case ofsulfuric acid:

[0047] Typically, some fraction of the monoester further reacts withisobutylene and ethylene to produce the diester:

[0048] Formation of the ethyl monoester, diethyl ester and mixed3,3-demethylbutyl/ethyl ester may compete with the formation of thedesired ester intermediates:

[0049] Alkylation reactions can also occur to produce various branchedchain hydrocarbon by-products of molecular weight characteristic ofinternal combustion engine fuels.

[0050] The extent of formation of such by-products can be minimized byappropriate control of the reaction conditions, including substantiallysimultaneous contact of the mineral acid medium with both isobutyleneand ethylene. If ethylene is brought into contact with sulfuric acid inthe absence of isobutylene, substantial formation of ethyl esters islikely to result. If contact between isobutylene and sulfuric acid ismaintained over any substantial time period in the absence of ethylene,formation of isobutylene dimers, polymers, and other alkylation productscan proceed.

[0051] The reactions may proceed at essentially any temperature, but arepreferably conducted in the cold to maximize yield of the desired esterproducts and minimize formation of “gasoline” by-products. Preferredreaction temperature are below 10° C., more preferably below about 0° C.For commercial manufacturing operations, the reaction temperature ismost preferably in the range of about −20° to about 0° C. It has beenobserved that the formation of the desired ester products

[0052] is nearly instantaneous. Accordingly, yields of desired productmight be further enhanced without material loss in productivity byoperation at even lower temperatures, e.g., −20° to −40° C., but attemperatures in the latter range the economic benefit in yield may bemore than offset by the economic penalty in refrigeration costs.

[0053] To maximize the yield of the desired ester products, the watercontent of the reaction medium is preferably maintained at a relativelylow level. Reaction rates also tend to decline with water content,though the reactions are in any case so rapid that the effect on rate isnot a significant economic factor. To achieve desired yields usingsulfuric acid, the strength of the acid as charged to the reaction zoneis preferably 90-100%, more preferably 95-100% by weight on anorganic-free basis. Even higher acid strengths may be desirable,extending into the oleum range. Higher sulfuric acid concentrations maybe useful not only in providing enhanced yields, but also in allowinguse of relatively inexpensive Fe/Cr alloys, or even carbon steel, asmaterials of construction for alkylation/esterification reaction processequipment. Alternatively, higher alloys, for example Ni/Mo alloys suchas Hastelloy B or Hastelloy C-276, may be used. In any event, to assurea given minimum acid strength at terminal conditions, it is desirable tointroduce acid of somewhat higher strength into the reaction, sinceconsumption of conjugate base in the esterification effectively resultsin dilution of the acid. Comparable limits on water content arepreferably imposed where acids other than sulfuric are used for thereaction.

[0054] Isobutylene may be introduced in liquid or gaseous form into thealkylation/esterification reaction zone, but is preferably introduced asa liquid to minimize heat load on the reactor refrigeration system.Ethylene is typically introduced as a gas; and an ethylene pressure ofbetween about 20 psig (275 kPa ga.) and about 200 psig (1400 kPa ga.),preferably between about 40 psig (550 kPa ga.) and about 140 psig (965kPa ga.) is maintained in the reaction zone. If the ethylene pressure issignificantly lower than about 40 psig, excessive formation ofhydrocarbon by-products may result, while at pressures above 140 psig,or especially above 200 psig, the extent of ethyl ester formation isincreased. Each of isobutylene and ethylene may be introduced eitherinto the head space of the reactor or below the surface of the condensedphase mixture. Optionally, either or both of isobutylene and ethylenemay be introduced as a solution in an organic solvent. Alternatively,ethylene may be introduced into the reaction zone in the liquid stateand the reaction conducted entirely in a system comprising two condensedphases.

[0055] The esterification/alkylation reaction may be conducted in eithera batch or continuous mode. To minimize oligomerization and formation ofby-product hydrocarbons, the concentration of isobutylene is preferablykept as low as feasible. In a batch reaction system, the reactor mayinitially be charged with mineral acid and solvent, after which theintroduction of isobutylene is commenced and the reaction zoneessentially simultaneously pressurized with ethylene. Isobutylene ispreferably introduced at a controlled rate of between about 0.01 andabout 0.5 liters per hour per liter of the combined condensed phasemixture. Whatever the mode by which isobutylene is introduced, or therate of its introduction, a molar excess of sulfuric acid vs.isobutylene is preferably maintained throughout the reaction in order tominimize isobutylene oligomerization. Preferably, the molar ratio ofsulfuric acid to isobutylene is maintained at at least about 1 at alltimes during the reaction, and the cumulative ratio of sulfuric acid toisobutylene introduced into the reaction zone is between about 2 andabout 1. An undue excess of sulfuric acid may result in excessiveformation of ethyl sulfate by-product. Introduction of ethylene isregulated to maintain an ethylene pressure in the range indicated above.

[0056] The reaction system is preferably agitated vigorously toestablish intimate interfacial contact for mass transfer to and/oracross the interface. Especially vigorous agitation may be indicatedbecause of the substantial difference between the density of the acidphase and the liquid organic phase. To provide the requisite interfacialcontact and mass transfer, conventional mixing principles may be appliedby those skilled in the art to provide appropriate geometry, shear, andpumping effects by selection of impeller type, rotational and tip speed,baffling, internal coils, dip tubes, etc. Further to facilitate masstransfer between the phases, phase transfer catalysts, such as tetraalkyl ammonium halides or hydroxides, alkyl phosphonium halides, benzyltrialkylammonium halides, or benzyl trialkylammonium hydroxides, may beincorporated into the reaction mixture.

[0057] In an alternative, semi-batch co-addition system, isobutylene andmineral acid are simultaneously introduced into the batch reactor,preferably at controlled rates while a pressurized ethylene atmosphereis maintained therein. Co-addition of isobutylene and acid tends tominimize competitive reaction of ethylene and acid. The solvent andminor fraction of the mineral acid are preferably charged to the reactorbefore co-addition begins. Optionally, solvent can be added togetherwith acid and isobutylene, in which instance the isobutylene and/orethylene may be introduced as a solution in the organic solvent. In afurther alternative, isobutylene and acid can be metered into an initialcharge consisting solely of solvent under ethylene pressure. Since thereaction proceeds essentially instantaneously, the batch is essentiallyfinished when addition of the condensed phase components is complete.Controlled co-addition of isobutylene and acid minimizes exposure ofunreacted isobutylene and ethylene to the acid phase, and may thereforetend to reduce the extent of by-product formation. After co-addition iscomplete, the reaction mass is removed from thealkylation/esterification reactor, but a reaction product heel may bemaintained in the reactor to provide a medium for reaction heat removalduring the co-addition phase of the succeeding batch, as describedimmediately below.

[0058] According to a modification of the co-addition process, the rateof sulfuric acid addition is controlled so that the entire charge ofacid is completed before the addition of isobutylene is complete. Inpractice of this embodiment of the invention, solvent and optionally asmall fraction of the acid, e.g., 1-25% of the overall acid requirement,are initially charged to the reactor, after which ethylene pressure isapplied the remainder of the acid and the isobutylene are metered intothe reactor at a relative ratio effective to complete the acid additionwell before addition of the isobutylene is finished. Thus, for example,the acid may be metered into the reactor in molar ratio to isobutyleneof between 1.1 and 2.5, preferably between about 1.2 and about 1.7, sothat addition of acid is completed one to five hours before completionof isobutylene addition. The reaction mixture is maintained underintense agitation during addition of acid and isobutylene. Thisalternative has been observed to be capable of providing a substantialreactor payload and a relatively high yield on mineral acid andisobutylene.

[0059] Whatever the schedule of isobutylene and acid addition, thecumulative charge of isobutylene and acid to a batch reactor, and theinstantaneous concentrations of isobutylene and acid, are preferablycontrolled to provide the greatest reactor payload consistent withsatisfactory yield of desired sulfate ester intermediate. If theisobutylene concentration is too high, excessive oligomerization ofisobutylene may occur and yields will suffer; if the isobutyleneconcentration is too low, productivity may suffer. In a batch orsemi-continuous system, cumulative acid to isobutylene ratio ispreferably between about 0.5 and about 4, preferably between about 1 andabout 2.

[0060] The alkylation and esterification reaction is substantiallyexothermic. For removal of exothermic heat, the autoclave may bejacketed and/or provided with internal cooling coils. Alternatively, orin addition, the condensed phase reaction mixture may be circulatedbetween the autoclave and an external heat exchanger. A refrigeratedcooling medium, e.g., brine solution or Syltherm, is passed through thejacket, coils and/or coolant fluid side of the external heat exchanger.Optionally, a liquefied refrigerant can be supplied to the jacket, coilsor external heat exchanger for removal of reaction heat by evaporativecooling. The reactor may be operated with full cooling throughout thereaction, and the temperature is controlled by regulating the rate ofintroduction of isobutylene into the reaction zone. In co-addition, therate of addition of isobutylene may be controlled in response totemperature, and the rate of addition of acid ratioed to the measuredrate of addition of isobutylene. Preferably, the capacity of the coolingsystem is designed to permit a relatively high rate of isobutyleneintroduction, e.g., in the range specified hereinabove. The reaction maybe conducted with a relatively low volumetric ratio of solvent phase toacid phase in the reactor, thereby maximizing the payload of desiredester product(s), which accumulate within the acid phase forming apregnant liquor comprising mineral acid and 3,3-dimethylbutyl esters.Generally, the batch is terminated when the sum of the monoester anddiester content of the pregrant liquor is between about 10 and about 90mole %, preferably between about 30 and about 60 mole %.

[0061] Because the alkylation and esterification reaction is so rapid,the reaction may optionally be carried out in a continuous stirred tankreactor (“CSTR”). The configuration of a CSTR is essentially the same asthat of a batch autoclave, and isobutylene and ethylene feeds may becontrolled on the same basis. Sulfuric acid is introduced at a ratesufficient to maintain a desired organic-free acid strength. Reactionmixture may be removed, e.g., from the reaction product stream that iscirculated through an external heat exchanger, at a rate controlled tomaintain a constant condensed phase level in the reactor. Sinceconversion is essentially instantaneous, productivity is governedessentially by heat transfer capacity. Residence time is not critical,but reactor volume should be sufficient to afford an inventory ofreaction mixture adequate for desired heat transfer capacity and stabletemperature control.

[0062] In accordance with a further option, the alkylation andesterification reaction may be carried out in a plug flow reactor.Various conventional forms of plug flow reactors can be used to conductthe reaction, with conventional heat transfer means being provided toremove the exothermic heat of reaction and maintain the temperature inthe desired range as described hereinabove.

[0063] The organic solvent used in the reaction is preferably a liquidaliphatic or aromatic hydrocarbon of moderate volatility, e.g., C₅ toC₁₈, that is compatible with the reaction, i.e., does not condense,polymerize or otherwise react with ethylene, isobutylene or the mineralacid. The solvent serves as a medium of absorption of ethylene, and as asolvent for isobutylene, through which the two olefins are brought intocontact with the acid phase in substantially uniform ratios to oneanother. The solvent also serves to remove alkylation by-products fromthe acid interface where the desired reaction is believed tosubstantially occur. It is preferred that the hydrocarbon solvent bestraight chain rather than branched, in order to minimize the formationof alkylation by-products. As noted, the reaction may be carried out ina batch or semi-batch system using a relatively low volumetric ratio ofsolvent to acid phase, e.g., less than 4 to 1, preferably less thanabout 3 to 1, more preferably between about 0.1 and about 2.5 to 1.Since dialkyl esters formed in the reaction have a substantialsolubility in aliphatic solvents, the solvent to acid ratio ispreferably maintained as low as possible to maximize reactor payload andyield.

[0064] It has further been discovered the yields on ethylene can beimproved by terminating introduction of ethylene after the reaction hasproceeded for a period sufficient to achieve substantial conversion ofisobutylene. For example, in the embodiment of the process comprisingco-addition of sulfuric acid and isobutylene to the reaction zone duringthe reaction, the introduction of ethylene may be substantially reducedor terminated after about 50%, preferably between about 70% and about80% of isobutylene has been charged to the reactor, typically withinabout 30 minutes before or after the time by which 95% of the sulfuricacid charge has been added, i.e., between 2 and 4 hours after theaddition of acid and isobutylene has been commenced. After ethyleneaddition is substantially terminated, ethylene pressure is allowed todecay as ethylene is consumed during the remainder of the reactioncycle, thereby minimizing the amount of ethylene lost when the reactoris vented after completion of the reaction. Especially favorable yieldscan realized by: controlling the relative rates of isobutylene andsulfuric acid addition at an integration average isobutylene/acid molarratio of between about 0.6 and about 0.75; controlling the overallweight ratio of organic solvent to sulfuric acid at less than about 0.5;adding sulfuric acid to the reactor over a 2 to 4 hour period in theratio to isobutylene discussed elsewhere herein; and terminating orsubstantially reducing ethylene addition not later than 30 minutes after95% of the sulfuric acid has been added.

[0065] In an alternative embodiment of the invention, it is possibly toomit introduction of solvent into the reactor, more particularly,without introducing solvent into the reaction zone from any extraneoussource. In effect, neat isobutylene may provide a medium for absorptionof ethylene, and vigorous agitation may be sufficient to maintainbalanced ratios of isobutylene to ethylene at the acid interface. Sincea degree of alkylation is essentially inevitable under most reactionconditions, a solvent phase may accumulate during the reactionregardless of whether solvent is initially introduced.

[0066] As indicated above, the pregnant liquor comprising the acid phaseof the alkylation/esterification reaction mixture typically containsbetween about 20 and about 50 mole % of the sum of 3,3-dimethylbutylhydrogen sulfate and di(3,3-dimethylbutyl) sulfate. As furtherindicated, minor amounts of various by-products may also be present. Ofthe mineral acid esters formed in the reaction, up to 50 mole %,typically 10 to 30 mole %, are diesters, the balance monoesters; and theoverall ratio of 3,3-dimethylbutyl to ethyl residues among the estersmay typically vary from about 50 to 1 to about 1 to 1. Additionally, onan organic basis, the pregnant liquor may typically contain betweenabout 0 and about 10 mole % bis(3,3-dimethylbutyl)ether, and betweenabout 0 and about 10 mole % diethyl ether. The H₂SO₄ acid content of thepregnant liquor is typically between about 25% and about 75% by weight,and the water content up to about 4% by weight, translating to aneffective acid strength in the range of about 65% to about 33% byweight. The organic phase of the alkylation/esterification reactionmixture may contain various hydrocarbon by-products, includingisobutylene dimer, olefinic oligomers and polymers, and “gasoline” rangehydrocarbon alkylation products. At the end of the reaction, thereaction product mixture is removed from the reaction zone, and the acidand organic phases of the mixture are separated, conveniently bygravity.

[0067] Solvent is preferably be recycled if provision is made for purgeof impurities and by-products. For example, all or a portion of thesolvent phase may be consistently or periodically distilled or a solventphase purge fraction removed from the process in a fractional amounteffective to control recycled impurities and by-products at anacceptable level. If desired, prior to distillation the solvent phasemay be contacted with an alkaline solution for removal and recovery ofany residual 3,3-dimethylbutyl hydrogen sulfate, anddi(3,3-dimethylbutyl) sulfate, and 3,3-dimethylbutyl ethyl sulfate fromthe organic phase.

[0068] Hydrolysis of the 3,3-dimethylbutyl esters is preferably carriedout as soon as practical after conclusion of thealkylation/esterification reaction. The acid phase pregnant liquor istransferred to a hydrolysis reaction zone where it is contacted withwater for hydrolysis of the 3,3-dimethylbutyl hydrogen sulfate,di(3,3-dimethylbutyl) sulfate, and 3,3-dimethylbutyl ethyl sulfateesters to 3,3-dimethylbutanol. Hydrolysis may be effected with orwithout addition of base by merely diluting the pregnant liquor withwater and heating the diluted mixture. Generally, water may be added ina volume roughly equal to the volume of the liquor, or more generally ina volumetric ratio to the liquor of between about 0.5 and about 4,thereby providing a hydrolysis feed mixture containing between about 5%and about 70% by weight 3,3-dimethylbutyl sulfate, between about 0 andabout 40% by weight di(3,3-dimethylbutyl) sulfate, between about 0% and20% by weight 3,3-dimethylbutyl ethyl sulfate, between about 10% andabout 60% by weight H₂SO₄, and between about 20% and about 65% by weightwater, equating to a diluted sulfuric acid strength of between about 13%and about 75% by weight on an organic free basis, and a water to totalmono and di 3,3-dimethylbutyl sulfate esters weight ratio of betweenabout 15 and about 0.25. During water addition, the pregnant liquor ispreferably maintained at a temperature not greater than 100° C., morepreferably less than about 50° C., most preferably less than about 25°C., by removing heat of dilution to a refrigerant or refrigeratedcooling fluid.

[0069] The diluted mixture is heated to a temperature of at least about75° C., preferably between about 90° and about 120° C. for a period ofbetween about 0.5 and about 12 hours, more preferably from about 1 toabout 4 hours. A phase separation occurs as the hydrolysis proceeds,yielding a lower spent acid phase and an upper organic hydrolyzate phasecontaining the desired 3,3-dimethylbutanol product. The product may berecovered from the organic hydrolyzate phase by distillation orliquid/liquid extraction. It has been discovered that residual acid inthe organic phase is detrimental in the distillation. In a batchprocess, it is preferred that this residual acid be neutralized byaddition of a base, e.g., by washing the organic layer with a 0.05 to 2N solution of alkali metal hydroxide or carbonate. Alternatively, analkline earth oxide or hydroxide may be added to affect removal ofexcess acidity in the form of a solid precipitate such as gypsum orMgSO₄. Distillation of the organic phase is preferably conducted atreduced pressure, e.g., 50 to 200 torr and a pot temperature of betweenabout 80° and about 150° C. Two major fractions are obtained, the firstof which is predominantly organic solvent with only trace proportions of3,3-dimethylbutanol. The second fraction is substantially3,3-dimethylbutanol with no more than negligible concentration, of >C₆alcohol by-products. Only a minor residue is retained in thedistillation pot.

[0070] The spent acid phase of the hydrolysis reaction mixture may bepurged from the process. Alternatively, it may be subjected to spentacid recovery processing as described below. Any residual3,3-dimethylbutanol can be recovered from the acid phase by solventextraction, and 3,3-dimethylbutanol thereafter recovered from theextract by distillation.

[0071] Although the hydrolysis step as described above is effective forthe preparation of 3,3-dimethylbutanol, various undesired by-productsmay be formed during the hydrolysis, including, e.g., ethanol,bis(3,3-dimethylbutyl) ether, diethyl ether, and the mixed ether. Also,the hydrolysis is an equilibrium reaction which cannot proceed in thepresence of a high concentration of alcohol. To minimize formation ofundesirable by-products and obtain maximum yields of3,3-dimethylbutanol, the hydrolysis is preferably effected by reactivedistillation, in which the desired alcohol product is distilled from thereaction mixture as it is produced. A hydrolysis feed mixture for thereactive distillation is provided by water dilution of the acid phasepregnant liquor obtained in the alkylation/esterification reactionmixture, at dilution ratios generally in the same range as discussedabove, but in any event sufficient for formation of an azeotrope of3,3-dimethylbutanol and water. The head pressure is not critical but thedistillation is preferably conducted either at atmospheric or reducedpressure in a range wherein an azeotrope of substantial3,3-dimethylbutanol content is produced. Heating the hydrolysis feedmixture in the distillation pot or reboiler effects both hydrolysis ofthe 3,3-dimethylbutyl hydrogen sulfate, di(3,3-dimethylbutyl) sulfate,and 3-3-dimethylbutyl ethyl sulfate esters to 3,3-dimethylbutanol, andremoval of the water/3,3-dimethylbutanol azeotrope as overhead vapor. Inatmospheric distillation, light ends may be removed at temperaturesbelow about 90° C., after which the 3,3-dimethylbutanol-rich azeotropeis distilled over at a temperature in the range of about 90° to 99° C.Although some rectification is desirable, only modest reflux and a fewtrays are indicated; and, if necessary, the azeotrope can be recoveredby a straight takeover distillation.

[0072] When the distillation temperature approaches 100° C., theoverhead vapor becomes essentially water only, and the distillation isterminated. The bottom product comprises the spent acid phase and aresidual oil. Both may be discarded; or directed to a spent acidrecovery operation. Recovered acid may be recycled to thealkylation/esterification reaction step. The oil phase may usefullyserve as a source of fuel for spent acid combustion.

[0073] Upon condensation, the 3,3-dimethylbutanol-rich azeotropefraction from the reactive distillation forms a two phase mixture, theupper layer of which comprises at least about 75%, ordinarily about 80to about 90%, by weight 3,3-dimethylbutanol, and typically containsabout 4 to 8% water, together with some ethanol, diethyl ether, andbis(3,3-dimethylbutyl) ether. The lower aqueous phase contains less than2%, generally less than about 1%, by weight of the desired3,3-dimethylbutanol product, together with some ethanol, and may bepurged from the process. On an organics basis, the upper phase maycomprise ≧90% by weight 3,3-dimethylbutanol with ≦10% by weight highboilers, i.e., >C₆ alcohols or residual esters. Consequently, withoutfurther refining, the upper phase may be used directly in thepreparation of 3,3-dimethylbutanal. Alternatively, the upper phase maybe subjected to further distillation, typically under vacuum, to improvethe assay of the 3,3-dimethylbutanol intermediate product to greaterthan 98%, with a high boiler content ≦2%, by weight.

[0074] Reactive distillation produces 3,3-dimethylbutanol in molaryields greater than 50%, typically 70% to 90% based on the sum of estersand diesters of 3,3-dimethylbutanol in the pregnant liquor. Sincehydrolysis of 3,3-dimethylbutanol esters releases mineral acid into thereaction mixture, thereby progressively increasing the mineral acidconcentration, it may be desirable to add a base to the reaction mixtureduring the hydrolysis to neutralize excess acidity. This may be done byaddition of a caustic or alkali metal carbonate solution to the reactionmass in response to measured increase in acidity. Optionally CaO, MgO,Ca(OH)₂ or Mg(OH)₂ may be added, thereby removing excess acidity byprecipitation of the solid CaSO₄ or MgSO₄ salt.

[0075] Where the pregnant liquor obtained from thealkylation/esterification reaction is substantially neutralized withbase before the reactive distillation, it is feasible to conduct thereactive distillation with a small proportion of water, sufficient onlyto effect the hydrolysis and generate the azeotrope. By condensation ofthe azeotrope, separation of the aqueous phase from the condensate, andreflux of the aqueous phase to the column, an inventory of watersufficient for both hydrolysis and azeotropic distillation ismaintained. For example, instead of a dilution ratio of 0.5 to 2.0 asdiscussed hereinabove, the pregnant liquor may be diluted with waterwithin a range of only about 0.1 about 0.5. Favorable results have beenobserved in conducting reactive distillation with water added in anintermediate ratio of about 0.3 to about 0.7 water/pregnant liquor.Substantial neutralization of the free acid prevents degradation of theproduct that might otherwise result from inadequate dilution.

[0076] Reactive distillation may be conducted in either a batch,semi-batch or continuous mode. In a continuous process, the pregnantliquor is continuously introduced into a distillation column comprisinga hydrolysis reaction zone. Heat for the reaction and distillation of3,3-dimethylbutanol is continuously supplied via a reboiler for thecolumn. Bottoms are circulated through a reboiler to supply heat for thereaction and distillation. Spent acid is continuously withdrawn from thereaction zone and discharged from the bottom of the column, e.g., inresponse to a sump level controller, at a rate equivalent to the netproduction thereof. Overhead vapor is continuously removed and condensedfor recovery of 3,3-dimethylbutanol. Light ends may be vented from thecondenser scrubbed and/or flared. Condensate is separated into a3,3-dimethylbutanol phase and aqueous phase in a continuous separatorfrom which the 3,3-dimethylbutanol phase is continuously decanted andaqueous phase continuously drained. The aqueous phase drains to a refluxsplitter where it is divided into a reflux stream and an forward flowstream. In batch reactive distillation, the pregnant liquor isintroduced into the distillation pot. Water may be charged at the startof the batch or introduced continuously or intermittently as the batchproceeds. The overhead condensate is allowed to separate and the aqueousphase is preferably refluxed to aid in the separation and promote thehydrolysis. If desired, fresh water can be introduced into top tray orother tray of the column. Alternatively, sulfate ester may be added to avessel containing hot water and the 3,3-dimethylbutanol formed onhydrolysis distilled off as an azeotrope.

[0077] In an alternative embodiment of the invention, acid esters of3,3-dimethylbutanol, e.g., bis(3,3-dimethylbutyl)sulfate or3,3-dimethylbutyl hydrogen sulfate are hydrolyzed by contact with anaqueous solution or dispersion of a base such as NaOH, KOH, Na₂CO₃,K₂CO₃, CaO, MgO, Ca(OH)₂, or Mg(OH)₂. The base is supplied in excess ofthe amount required for to neutralize the free acid in thealkylation/esterification reaction mixture and the acid released in thehydrolysis so as to establish a pH sufficient to promote the hydrolysis.

[0078] Further in accordance with the invention, 3,3-dimethylbutanol maybe converted to 3,3-dimethylbutanal by catalytic dehydrogenation. Forexample, a suitable catalyst for the dehydrogenation may be prepared,optionally in situ, by contacting 3,3-dimethylbutanol with astoichiometric oxidation reagent comprising a metal oxide such as cupricoxide, cuprous oxide or a mixture of Cu(I) and Cu(II) oxides. Contactingthe 3,3-dimethylbutanol with the metal oxide catalyst results in thedesired conversion of 3,3-dimethylbutanol to 3,3-dimethylbutanal byoxidative dehydrogenation in a stoichiometric redox reaction whichconcomitantly reduces the metal oxide oxidizing agent to a reduced formcomprising an active phase effective for the further anaerobicdehydrogenation of an alcohol to an aldehyde. Thereafter, with minimalif any interruption, contact of 3,3-dimethylbutanol with the catalystcan be continued for continuing production of 3,3-dimethylbutanal.

[0079] Other catalysts useful in the catalytic dehydrogenation includesilver, gold, platinum, palladium, and a Pt/Sn alloy Cu/Zn. To extendthe active surface area of the catalyst active phase, the catalyst maybe supported on conventional catalyst carrier such as carbon, alumina,silica, mixtures of silica and alumina, titania, zirconia, zeolite,kieselguhr, baryte, controlled pore glass (“CPG”), etc. Co-ordinationcompounds of Ru, Cu, Pt or Pd may also be effective.

[0080] Essentially any catalyst effective for the dehydrogenation ofalcohols to corresponding aldehydes may be used in the process. Such mayinclude, for example, Cu—ZnO, Ag—Cu, ZnO, Co(II) molybdate, vanadiumpentoxide, Ni, Ir, Ru, Re, Co, Zr, etc. Also see Augustine,“Heterogeneous Catalysts for the Synthetic Chemist,” Marcel Dekker,Inc., 1996, pp. 430 to 472. Among the additional catalysts thereindisclosed which may be useful in the dehydrogenation reaction are RaneyNi, Ni boride, Pto₂, Cu—CrO, Pd/C, Pd black, Pd/baryte, Ir/C,FeCl₃-doped Ru/C, Ru—Sn, Co boride, Co/alumina, Co—Zr/alumina, Raney Co,Ag—Fe, Ag—Zn, pre-reduced Re₂O₇, Pt/C, Pt/nylon, Re/CPG, Cu chromite,etc.

[0081] Where 3,3-dimethylbutanol is to be used as an intermediate for apharmaceutical, or for a food product such as neotame, a catalyst ispreferably selected which is substantially non-toxic. Catalysts whichare effective for the reaction and substantially non-toxic includemetallic copper, copper oxide and reduced copper oxide, as well asCa—ZnO, Co, V, Ni, Ir, Ru, Re, etc. Chromium containing catalysts arepreferably avoided.

[0082] The transitory stoichiometric oxidation reaction is exothermic,so appropriate provision must be made for removal of reaction heat.Preferably, the stoichiometric oxidation is conducted at a temperaturein the range of between about 150° and about 350° C. Stoichiometricoxidation reaction may be conducted in a slurry reaction system in whichthe metal oxide catalyst is initially suspended in an agitated3,3-dimethylbutanol reactant medium, optionally including a high boilinginert solvent such as bis(3,3-dimethylbutyl)ether, or vapor phase3,3-dimethylbutanol may be passed over a fixed or fluid bed of metaloxide and therein converted to 3,3-dimethylbutanal. Since the functionof this phase of the process is merely to prepare the catalyst, there islittle if any criticality or importance to catalyst slurry concentrationor alcohol in solvent concentration in a liquid phase system, or to thespace velocity or other parameters of a fixed bed or fluid bed vaporphase system.

[0083] In a slurry reaction system for the dehydrogenation reaction ofthe invention, a particulate catalyst, such as metallic copper isslurried in a liquid dehydrogenation reaction medium comprising eitherneat 3,3-dimethylbutanol or a solution of 3,3-dimethylbutanol in anappropriate solvent, e.g., an ether such as diphenyl oxide. Particulatecatalyst is slurried in the liquid reaction medium in a proportion of atleast about 1% by weight, preferably between about 5% and about 20% byweight based on the 3,3-dimethylbutanol charge. The dehydrogenationreaction is conducted at a temperature of at least about 100° C.,typically 100° C. to 400° C., preferably at least about 200° C., morepreferably between about 275° and about 350° C., for a period sufficientfor the reaction, typically in the range of 100 or more hours. Since thedehydrogenation reaction is endothermic, the temperature is preferablycontrolled at the desired level by introduction of heat by passage ofsteam or other heating medium through a jacket on the reactor or coilscontained therein. The total pressure is preferably as low as feasible,more preferably not greater than about 100 psi (690 kPa) higher than thevapor pressure of the liquid reaction medium at the reactiontemperature, more preferably not higher than 100 psig. An inert gas ispreferably sparged into the reacting liquid to aid in displacinghydrogen therefrom. Hydrogen partial pressure is preferably below 100psig. The presence of a minor proportion of water may be desirable topromote activity of the catalyst by facilitating the removal of reactionproduct from the active sites of the catalyst. The presence of water mayalso marginally improve the selectivity of the reaction for3,3-dimethylbutanal. After the reaction is completed, the catalyst isseparated from the reaction mixture by filtration, and the3,3-dimethylbutanal product stripped from the solvent. Catalystrecovered by filtration may be recycled for use in subsequentdehydrogenation batches.

[0084] A liquid phase dehydrogenation reaction may be operated in areactive distillation mode for removal of product 3,3-dimethylbutanal.By removal of hydrogen and product aldehyde from the reaction mixture,reactive distillation is effective to drive the equilibrium reactionforward. Although reactive distillation can provide for effectiveremoval of the product 3,3-dimethylbutanal, a relatively high totalpressure should be maintained to minimize stripping of3,3-dimethylbutanol. Lower pressures can be tolerated but requirecondensation of 3,3-dimethylbutanol from the exit hydrogen stream andreflux to the reactor, thereby increasing the heat demands of theendothermic reaction system.

[0085] Although a liquid phase, slurried catalyst dehydrogenationreaction is effective for preparation of 3,3-dimethylbutanal, it ispreferred that the reaction be conducted in vapor phase over a fixed orfluid catalyst bed comprising a tabular or particulate dehydrogenationcatalyst. In the preferred dehydrogenation process, a feed stream isprovided comprising at least about 0.5% by volume 3,3-dimethylbutanol,preferably between about 1% and about 25% by volume, more preferablyabout 2.5% to about 10% by volume in a carrier gas such as helium,nitrogen, carbon dioxide, steam, or mixtures thereof. Optionally, thefeed gas diluent may consist solely or predominantly of steam. It isfeasible for the concentrations of 3,3-dimethylbutanol to be higher thanspecified above, but relatively high temperatures are required toestablish a favorable reaction equilibrium, as a result of whichconversions at high concentration are limited by endothermic cooling. Toan extent, it is possible to compensate for endothermic cooling byintroducing the feed stream into the reactor at even higher temperaturesthan required for favorable equilibria, e.g., 500° C., in which instanceit may be feasible to operate the reactor adiabatically. However, highfeed gas temperature may cause sintering or other adverse effects on thecatalyst. However, introduction of the feed gas at a temperature nearthe upper end of the preferred 250° to 375° C. operating range isdesirable in any case to maintain the temperature in that range througha maximum portion of the reaction zone. The inert gas serves as a heatballast helping to maintain the desired temperature. The dehydrogenationfeed stream is passed through a dehydrogenation reaction zone comprisinga fixed or fluid bed containing catalyst bodies having an active phasecomprising a dehydrogenation catalyst. The vapor phase is preferablysubstantially free of molecular oxygen. The reaction is preferablyconducted at a temperature of at least about 200° C., more preferably inthe range of between about 250° and about 375°, most preferably betweenabout 275° to 345° C. Temperatures in the upper portion of the latterrange, e.g., 305° to 330° C. provide more favorable equilbria, buttemperatures in the lower end of the range, e.g., 275° to 295° preservecatalyst activity over a longer catalyst life. To depress formation ofether and olefin by-products, it may be desirable to include steam inthe feed gas to the dehydrogenation reactor. Relatively hightemperatures within these ranges provide a higher equilibrium constantfor the reversible dehydrogenation, and thus favor high conversions to3,3-dimethylbutanal. The total pressure is maintained at no greater thanabout 100 psig (690 kPa), preferably between about 0 psig (0 kPa) andabout 25 psig (170 kPa), and the hydrogen partial pressure is maintainedat less than about 100 psig (690 kPa), preferably between about 5 psig(35 kPa) and about 20 psig (140 kPa). Both reaction equilibrium andselectivity become more favorable as the pressure decreases, but it isgenerally preferred to operate at least at atmospheric pressure tominimize velocity and pressure drop in the catalyst bed, and to preventair from leaking into the hydrogen-containing reaction product stream.

[0086] Preferably, the catalyst bodies comprise a metal oxide activephase on an inert support.

[0087] The reactor is operated at a space velocity of at least about0.25 sec⁻, preferably between about 0.5 and about 2 sec⁻¹ and a linearvelocity of about 0.2 to about 5 ft./sec., preferably about 0.8 to about2.5 ft./sec. The activity and selectivity of preferred catalysts aresufficient so that the volume of the catalyst bed can be sized for asingle pass conversion to 3,3-dimethylbutanal of at least about 50%,preferably between about 80% and about 100%. Residence time required forsuch conversion within the above noted range of space velocities is onlyabout 0.1 to about 10 seconds. Typically the reaction gas exiting thedehydrogenation reaction zone contains between about 50 and about 98% byvolume 3,3-dimethylbutanal and between about 50 and about 2% by volume3,3-dimethylbutanol, in a ratio of at least about 1, more typicallybetween about 4 and about 49 moles 3,3-dimethylbutanal to moles3,3-dimethylbutanol. Where a metallic copper or other preferred catalystis used, conversions greater than 50% may be maintained in sustainedoperations of over 30 days without regeneration of the catalyst.

[0088] Although the activity of preferred catalysts is sufficient toachieve substantially quantitative conversion in a very short residencetime, a non-linear relationship has been discovered between the catalystcharge and the rate of catalyst deactivation. A catalyst charge justsufficient to provide equilibrium conversion in the first few hours ofoperation has been observed to deactivate rather rapidly beginningalmost immediately after startup. However, a catalyst charge that issignificantly larger than the minimum required to achieve equilibriumdeactivates much more slowly, so as to extend catalyst lifedisproportionately to the additional charge of catalyst. As described infurther detail in the working examples set out below, this observationtranslates into a most preferred space velocity toward the low end ofthe preferred range described above, i.e., below 2.0 sec⁻¹, e.g., fromabout 1.0 to about 1.5 sec⁻¹. Since catalyst performance relatesprimarily to the flow of 3,3-dimethylbutanol rather than total flow, thetotal flow rate through the reactor is determined primarily by competingconsiderations of temperature control and pressure drop; but in any casethe product of space velocity and the volume fraction of3,3-dimethylbutanol in the feed gas is most preferably controlled in therange of about 0.05 to about 0.08 (cc alcohol)(cc feed gas-sec)⁻¹.

[0089] While high catalyst loading provides exceptional benefits incatalyst life, it can also result in relatively poor selectivity duringthe reactor startup phase. It has been discovered that early selectivitycan be improved by initial operating at relatively low temperature, e.g.240° to 270° C. during a catalyst phase in period, and thereafteroperating at a desired value for optimal conversion, preferably between275° C. and about 345° C. The phase in period is long enough so that ayield of 3,3-dimethylbutanol of at least 85%, preferably at least about88%, more preferably at least about 90%, is achievable from about 90minutes after the beginning of the phase in period until a turnoverratio of at least 5 moles 3,3-dimethylbutanal per mole catalyst activephase has been realized. Typically, the requisite phase in period is oneto four hours. Once any transient effect of startup has been traversed,the selectivity can be slightly better at higher vs. lower catalystloading.

[0090] As noted, the anaerobic dehydrogenation reaction is endothermic.Thus, it is necessary or desirable to dilute the alcohol reactantsubstantially with an inert gas, as described hereinabove. The inert gasserves both: as a heat source, which minimizes temperature drop acrossthe reactor, so that the equilibrium coefficient deteriorates as littleas possible from reactor inlet to reactor exit; and as a diluent, whichenhances equilibrium conversion at a given reaction temperature. It mayfurther be desirable to introduce supplementary heat into the reactionsystem, either by surface heat transfer or by reheating the gas throughintroduction of hot diluent gases at discrete points along the route ofpassage of reacting gases through the catalytic dehydrogenation zone.For example, the reaction can be conducted over a fixed bed that isarranged in a plurality of stages in series and contained in a reactionvessel having a chamber substantially free of catalyst between asuccessive pair of said stages with respect to the passage of reactiongas through the reactor. A supply of heated gas is provided to theinterstage chamber for reheating reaction gas entering said chamber fromthe stage immediately upstream of the chamber. Typically, the reactormay contains two or more catalyst stages and a plurality of suchinterstage chambers that are substantially free of catalyst, each ofsaid chambers being located between a successive pair of catalyststages. A supply of heated inert gas may be provided to each of theplurality of interstage chambers for reheating reaction gas enteringsuch chamber from the stage immediately upstream thereof. Alternatively,the feed gas is heated to a temperature sufficient so that the reactioncan proceed to the above indicated conversions under adiabaticconditions.

[0091] Alternatively, the dehydrogenation catalyst may be packed in thetubes of a shell and tube heat exchanger. A feed gas having thecomposition described hereinabove may be preheated in any convenientmanner to a temperature effective for the dehydrogenation. A heattransfer fluid, e.g., molten salt bath is passed through the shell sideof the exchanger to supply heat for the reaction and maintain the gastemperature in a range within which the reaction equilibrium isreasonably favorable, e.g., 200° C. to 400° C. Per a furtheralternative, the reaction tube(s) can be immersed in a sand bath that isin turn directly heated by contact with a flue gas that is produced byburning a hydrocarbon fuel or by electrical heating. In a still furtheralternative, flue gas may be injected into the process gas stream atpoints spaced along the reaction flow path to maintain the reactiongases at the desired temperature. As noted, adiabatic operation isanother option, but conversions are limited by the effect of endothermiccooling on the terminal reaction temperature, even at feed gastemperatures so high that they may cause damage to the catalyst in theupstream portion of the bed.

[0092] The dehydrogenation reaction product gas is cooled to condense3,3-dimethylbutanal product and any unreacted 3,3-dimethylbutanoltherefrom. Refrigeration to a temperature of about −25° C. to about 0°C., preferably about −18° C. to about −8° C., is desirable to obtainrecovery of 3,3-dimethylbutanal in good yield. Optionally, the productgas may be compressed, e.g., to between about 10 and about 1000 psig, toallow condensation at higher temperature. The condensate may then be ordistilled for separation of the product 3,3-dimethylbutanal from theintermediate 3,3-dimethylbutanol. According to a further option, thereaction product gas may be passed through a partial condenser forremoval of 3,3-dimethylbutanol, followed by a total condenser.Condensate from either or both condensers is then distilled to refinethe 3,3-dimethylbutanal product. Distillation for refining of3,3-dimethylbutanal can be conducted in either a batch or continuousmode. A 98% assay 3,3-dimethylbutanal fraction may be obtained.

[0093] Although purification of the reaction product condensate may bedesirable in some instances, it is not generally necessary. Unlike theproduct of various prior art processes for the preparation of3,3-dimethylbutanal, aldehyde produced in accordance with the process ofthis invention, as described hereinabove, is substantially free ofimpurities that create significant adverse effects in the reductivealkylation reaction for the synthesis of Neotame. More particularly, onan organics basis, the condensate contains less than 1% by weight of thecorresponding acid (t-butylacetic acid). Where 3,3-dimethylbutanal isproduced by stoichiometric oxidation in the presence of a free radicaloxidizing agent, purification of the reaction product by distillationencounters formation of both an alcohol water azeotrope and analdehyde/water azeotrope, each of which is also difficult to remove. Byobviating the need for purification, the process of the presentinvention avoids the need for resolving these azeotropes.

[0094] According to a still further alternative, the reaction gasexiting the dehydrogenation reactor may be contacted with an absorbentfor 3,3-dimethylbutanal. For example, the gas may be passedcountercurrently to a liquid absorbent stream in an absorber e.g. atower containing means such as rings, saddles or other packing materialfor promoting mass transfer of 3,3-dimethylbutanal from the gas to theliquid phase. A solution of 3,3-dimethylbutanal in the absorbent exitsthe bottom of the tower. Absorbents useful in this embodiment of theinvention include organic solvents such as methanol, ethyl acetate,tetrahydrofuran, or methyl isobutyl ketone. 3,3-Dimethylbutanal maystripped from the rich absorbent stream, e.g., under vacuum or byintroduction of live steam. Alternatively, the organic solution of thealdehyde may be introduced as such into a process for the manufacture ofneotame or other product for which 3,3-dimethylbutanal may serve as anintermediate.

[0095] In a still further alternative embodiment, 3,3-dimethylbutanaland any unreacted 3,3-dimethylbutanol may be condensed from thedehydrogenation reaction gas stream by quenching in water, for example,by causing the gas stream to flow countercurrently to an aqueousquenching stream in a packed or tray tower, or by introducing the gasbelow the surface of an aqueous quenching bath. Thereafter3,3-dimethylbutanal is allowed to separate from the aqueous quenchingmedium; and organic product phase may then be purified bycrystallization or distillation, or used directly in the manufacture ofNeotame.

[0096] In the process of the invention it has been found that catalystsfor the dehydrogenation of 3,3-dimethylbutanol remain highly active overruns which extend well beyond those reported in the prior art.Productivity and yields remain substantially stable over such extendedperiods of operation. Turnover ratios of 5, 10, 15 or more moles3,3-dimethylbutanal per mole catalyst active phase are readily achievedwithout interruption of the reaction for regeneration of the catalyst.Moreover, each such turnover ratio may be realized at a yield of3,3-dimethylbutanal which is at least 80%, more typically 90%, 95% or98% of the initial or maximum yield achieved during the course of acatalyst run. “Turnover” as referred to herein means moles productproduced per total moles of the active phase of the catalyst, withoutreference to the actual number or density of active sites in the activephase. In the case of a catalyst structure having more than one phase,e.g., a metal or metal oxide catalyst on an inert support, “catalystactive phase” means only the phase containing the active sites at whichthe reaction is conducted or initiated.

[0097] Where an anaerobic dehydrogenation is conducted at a site wherehydrogen may be used in the reduction of a hydrogen acceptor, it may befeasible to conduct the dehydrogenation in the presence of the hydrogenacceptor, thereby making effective use of the hydrogen, possibly insitu, and potentially driving the equilibrium reaction in the desireddirection under conditions that might not otherwise be conducive to thepurpose, e.g., at relatively low temperature, high 3,3-dimethylbutanolconcentration, or high pressure. For example, it may be feasible todrive the reaction quantitatively at a temperature in the range of 200°to 250° C. and/or at 3,3-dimethylbutanol concentrations in excess of 50mole %. If the 3,3-dimethylbutanol to 3,3-dimethylbutanal conversiontakes place entirely in the liquid phase, the reaction may be promotedby the presence of a gas phase which functions as a hydrogen acceptor,or vice versa. Typical hydrogen acceptors include ketones, aldehydes(other than the desired product), or olefins.

[0098] Although 3,3-dimethylbutanol is preferably converted to3,3-dimethylbutanal by anaerobic dehydrogenation as described above,other methods may be employed for this conversion. For example, thereaction can be carried out by aerobic dehydrogenation according toprocess schemes comparable to those discussed above for anaerobicdehydrogenation. Oxidative dehydrogenation is an exothermic reactionwhich proceeds irreversibly. In accordance with this alternativeprocess, a vapor phase mixture of 3,3-dimethylbutanol and anoxygen-containing gas can be passed over a fixed or fluid catalyst bed,or an oxygen-containing gas can be introduced into a slurry of catalystin a liquid phase comprising 3,3-dimethylbutanol. In a vapor phasereaction system, the feed gas preferably contains oxygen in a proportionbetween about 1% and about 20%, preferably between about 5% and about10%, by volume, and 3,3-dimethylbutanol in a proportion of between about5% and about 10% by volume. In the aerobic process, dehydrogenation iseffected oxidatively, forming water rather than hydrogen as a by-productof the reaction. Catalysts useful in oxidative dehydrogenation includemetal oxides such as copper oxide, zinc oxide or a copper oxide/zincoxide mixture. In oxidative dehydrogenation, the metal oxide is believedto participate in a redox reaction with the 3,3-dimethylbutanolsubstrate, forming 3,3-dimethylbutanal and water with concomitantreduction of the metal oxide to a metallic or other reduced state, as inthe stoichiometric reaction as described above. Reoxidation with oxygenfrom the gas stream restores the activity of the catalyst for theoxidative dehydrogenation. In this manner, the aerobic catalytic processdiffers from the stoichiometric process in which the oxidizing agent isconsumed in the reaction and, if regenerated at all, is regeneratedoff-line. Oxidative dehydrogenation is a highly exothermic reaction thatis preferably conducted at a temperature of between about 150° about250° C., i.e., somewhat lower than the optimal temperature for anaerobicdehydrogenation. Because of a tendency for over-oxidation to3,3-dimethylbutanoic acid, oxidative dehydrogenation may not provide theyields afforded by the anaerobic process. On the other hand, theexothermic nature of the reaction not only allows the aerobic process tobe run at relatively lower temperature, but also at higher3,3-dimethylbutanol concentration, in excess of 50 mole %, withoutadverse equilibrium effects.

[0099] Advantageously, the oxidative reaction may be carried out in atubular reaction system comprising the tubes of a shell and tube heatexchanger. Feed gas comprising 3,3-dimethylbutanol and oxygen isintroduced into the tubes, which are packed with an appropriate catalystfor the reaction. A heating fluid such as molten salt is circulatedthrough the shell side of the heat exchanger for removal of the heat ofthe reaction. Alternatively, the temperature of the reaction gases maybe maintained in accordance with any of the various stratagems describedabove for anaerobic dehydrogenation. Thus, the reaction system iscomparable to one of the alternative systems described above foranaerobic dehydrogenation, but the molten salt bath or fluidized sandbath serves as a cooling rather than heating medium. 3,3-Dimethylbutanalis recovered from the reaction gas by condensation or absorption asdescribed above. Optionally, the reaction gas may be compressed prior tocondensation or absorption. Separation of the desired3,3-dimethylbutanal product is obtained by distillation of condensate orstripping from rich absorbent solution, as further describedhereinabove.

[0100] In still further alternative embodiments of the overall processof the invention, 3,3-dimethylbutanol is produced initially by eitherreduction of 3,3-dimethylbutanoic acid according to the proceduredescribed in J. Org. Chem., Vol. 46, 1981, pp. 2579-2581 for thepreparation of ethanol and phenylethanol, by hydrolysis of a1-halo-3,3-dimethylbutane as described in J. Am. Chem. Soc., Vol. 73, p.555, or by conversion of the epoxide to the alcohol per the methoddescribed in Neftelehimiyn, 19, pp. 762-766 (1979). In the reduction of3,3-dimethylbutanoic acid, an alkali metal borohydride serves as apreferred reducing agent. Alternatively, 3,3-dimethylbutanoic acid maybe reduced to 3,3-dimethylbutanol by catalytic hydrogenation.

[0101] 3,3-Dimethylbutanoic acid may be prepared in accordance with themethod described in Synthesis, 1985, pp. 493 to 495 wherein vinylidenechloride is reacted with t-butanol in sulfuric acid, followed byhydrolysis. Alcoholysis produces an ester of the alcohol and3,3-dimethylbutanoic acid, which may be reduced to 3,3-dimethylbutanol.The fatty alcohol may be produced from the ester by hydrogenation underhigh pressure and temperature. See “Oils and Fats Manual,” LavoisierPublishing, 1996, pp. 1083 to 1084. Hydrogenation of the acid is anattractive route to 3,3-dimethylbutanol because it is typically highlyefficient and does not necessarily require a solvent. Non-catalyticreducing agents for 3,3-dimethylbutanoic acid include Li Al hydride andNa borohydride.

[0102] Hydrolysis of 1-halo-3,3-dimethylbutane may be carried out in thepresence of base at a temperature greater than about 200° C., preferablybetween about 200° to about 250° C. A moderately strong base such as analkali metal carbonate is effective for the reaction, but tends togenerate very high pressure due to the release of carbon dioxide.Preferably, therefore, a Group II metal oxide such as zinc oxide may beused to promote the hydrolysis. Alternatively, an alkali metal salt ofan organic acid may be used, e.g., K acetate, thereby producing an esterof 3,3-dimethylbutanol and the acid, which may be hydrolyzed to3,3-dimethylbutanol in the presence of a strong base such as NaOH orKOH.

[0103] According to a further alternative, 1,2-epoxy-3,3-dimethylbutanemay be formed by epoxidation of 3,3-dimethylbutene, with an alkali metalhypohalite, such as Na hypochlorite or dimethyldioxirane. Hydrogenationof the epoxide in the presence of a platinum metal or transition metalcatalyst, e.g., Pt, Pd or Ni, yields a mixture of 3,3-dimethylbutanoland 3,3-dimethyl-2-butanol, under optimal conditions in an 8:2 ratio. Inconducting the hydrogenation, a solution of1,2-epoxy-3,3-dimethyltbutane is charged to an autoclave in a solventsuch as an alkane such as hexane or heptane, a lower alcohol such asmethanol or ethanol, an ester such as methyl or ethyl acetate or anether such as tetrahydrofuran. A catalyst such as Raney Ni, in aproportion of about 0.5 g to about 1 g/mL 3,3-dimethylbutene oxide, orPd/C, in a proportion of about 0.001 to about 0.1 g Pd/mL3,3-dimethylbutene oxide, is slurried in the charge solution. Reactionis carried out under vigorous agitation at a temperature of betweenabout 50° and about 200° C., preferably between about 90° and about 160°C., and a hydrogen pressure of between about 50 and about 3000 psig,preferably between about 100 and about 1000 psig.

[0104] In a further method, an organometallic reagent such as a t-butylGrignard reagent or t-butyl lithium is reacted with ethylene epoxide atlow temperature to yield 3,3-dimethylbutanol. Preferably, the reactionis conducted in a solvent for the reactants such as diethyl ether,pentane, heptane, t-butyl methyl ether, toluene or tetrahydrofuran.Because organometallic reagents are sensitive to moisture and oxygen,the reaction is carried out under an inert atmosphere, e.g., helium,argon or nitrogen. The reaction should be carried out at lowtemperature, e.g., in the range of between about −100° and about −50° C.After an appropriate reaction period, e.g., 30 minutes to 3 hours, thereaction solution is allowed to warm to room temperature and quenchedwith a mineral acid such as sulfuric acid. The aqueous and organicphases are then separated, and the aqueous layer extracted with solventfor recovery of residual alcohol product. The combined organic layersmay then be washed with water and dried with a desiccant such as MgSO₄.The solvent is removed and the residue distilled to yield the3,3-dimethylbutanol product.

[0105] While all of the above described methods for the preparation of3,3-dimethylbutanol may be used in the processes of the invention forpreparation of 3,3-dimethylbutanal and Neotame, 3,3-dimethylbutanol ispreferably prepared by an alkylation/esterification reaction ofethylene, isobutylene and a mineral acid, as described in detail above.

[0106] As noted, 3,3-dimethylbutanal is useful as an intermediate in thepreparation of neotame. As described in U.S. Pat. No. 5,728,862,expressly incorporated herein by reference,N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl estermay be prepared by treating a mixture of aspartame and3,3-dimethylbutanal in an organic solvent with hydrogen in the presenceof a hydrogenation catalyst at a temperature and pressure effective toform the desired product. Alternatively, 3,3-dimethylbutanal may beadded to a mixture of aspartame and sodium cyanoborohydride as describedin U.S. Pat. No. 5,480,668, also expressly incorporated herein byreference.

[0107] Particular embodiments of the overall process for producing3,3-dimethylbutanal are illustrated in FIGS. 7 and 8. Referring to theblock diagram of FIG. 7 and, more particularly, to the equipment itemsreferenced on the flowsheet of FIG. 8, sulfuric acid is transferred froma supply tank 3 by a transfer pump 7 to an alkylation/esterificationreactor 1. Reactor 1 is provided with a cooling jacket 5 and an agitator9. Isobutylene is transferred from a supply tank 15 through a condenser25 which is chilled by heat transfer to a refrigerated brine solution,and by an isobutylene transfer pump 17 to reactor 1. Heptane is suppliedto reactor 1 from a recovered heptane tank 19 via a heptane transferpump 21. Additional makeup heptane, as needed, is supplied to thereactor from a heptane storage tank 11 via a heptane transfer pump 13.Ethylene from a source 23 is introduced into the head space of reactor 1at a pressure effective for the reaction, as described hereinabove.Optionally, ethylene can be sparged below the surface of the mixture ofcondensed phases, i.e., acid and heptane.

[0108] In reactor 1, sulfuric acid, ethylene and isobutylene are reactedunder intense agitation to form a reaction mixture comprising a pregnantliquor comprising 3,3-dimethylbutyl hydrogen sulfate,di(3,3-dimethylbutyl) sulfate, and 3,3-dimethylbutyl ethyl sulfate insulfuric acid, and an organic phase comprising heptane and alkylationby-products. The reactor may be operated in either batch or continuousmode. The flowsheet of FIG. 8 is adapted for operation as a batch orsemi-continuous reactor in which the heptane is initially charged to thereactor with all or a portion of the sulfuric acid. Ethylene pressure iscontrolled at a constant value by a pressure regulator 43 in a vent linefrom reactor 1, and isobutylene liquid is metered into the reactor,along with the remainder of the sulfuric acid if the all the acid hasnot been initially charged to the reactor. Alternatively, reactor 1 maybe operated as a continuous stirred tank reactor into which sulfuricacid and a heptane solution of isobutylene are continuously orintermittently introduced under a constant pressure of ethylene, andfrom which the alkylation/esterification reaction mixture continuouslyor intermittently withdrawn. A gas separator 45 can be used to minimizeliquid entrainment. If desired, the vented gas can be collected,compressed and recycled. Ethylene pressure may be controlled, e.g., byuse of a variable speed compressor or by a pressure regulator betweensource 23 and reactor 1.

[0109] Degassed alkylation/esterification reaction mixture withdrawnfrom reactor 1 is transferred via a pump 27 to a liquid/liquid separator29. The upper organic phase is removed from separator 29, flows into afeed tank 31 and is thence transferred to a heptane recoverydistillation column 33 via a column feed pump 35. The heptane recoverysystem is designed such that the distillation operation can be operatedin batch or continuous mode. FIG. 8 illustrates a column with threerectification trays and three stripping trays. Heat is supplied via areboiler 37, and overheads are condensed in a condenser 39, flowing to acondensate drum 41 and a reflux splitter (not shown). The column isoperated at a reflux convenient to the separation and the remainder ofthe overhead condensate flows to a recovered heptane receiver 19.Recovered heptane is recycled via a heptane recycle pump 21 to reactor1.

[0110] Pregnant liquor drawn from the bottom of separator 29 istransferred via a pump 47 to a hydrolysis reactor 49 which is providedwith a heating jacket 51 and an agitator 53. Deionized water isintroduced into reactor 49 from a water head tank 55. Water reacts withthe sulfate esters of 3,3-dimethylbutanol to produce 3,3-dimethylbutanolwhich is distilled out of the hydrolysis reaction mixture by heatsupplied from jacket 51. Spent acid is withdrawn from the bottom ofreactor 49 and transferred via a spent acid pump 57 to a neutralizationreactor 59 which is also provided with a jacket 61 and an agitator 63.Caustic soda is added from a head tank 65 to neutralization reactor 59to neutralize the spent acid. The resultant neutral salt solution issent to aqueous waste by waste pump 67. The salt solution can be furtherdiluted with water, if desired.

[0111] Overhead vapor from the reactive distillation reactor is passedthrough a packed fractionation column 69 operating on internal refluxonly. Vapor exiting the top of column 69 is condensed in an alcoholcondenser 71, and the condensate flows to a receiver/separator 73. Theaqueous phase which contains less than 1% by weight 3,3-dimethylbutanolis drawn off the bottom of separator 73, and is transferred via a pump75 to neutralization reactor 59 for ultimate disposal. The upper phase,typically comprising about 80 to 90% by weight 3,3-dimethylbutanol and 4to 8% by weight water, flows by gravity from separator 73 to adistillation feed tank 77, and thence via a column feed pump 79 to adistillation column 81 for isolation of 3,3-dimethylbutanol, obtained asa distillate from the column. As shown, column 81 comprises threerectification trays and three stripping trays. The distillation systemfurther comprises a reboiler 83, an overheads condenser 85, a condensatedrum 87 and a reflux splitter (not shown). The column is operated at areflux convenient to the separation and the remainder of the overheadcondensate flows to a 3,3-dimethylbutanol product receiver 89, whence itmay be transferred by pump 91 to an oxidation or dehydrogenation reactorfor conversion of 3,3-dimethylbutanol to 3,3-dimethylbutanal.

[0112] Bottoms from columns 81 and 33 are transferred via bottoms pumps93 and 95 respectively to an organic waste tank 97. A pump 99 sends thecollected bottoms to organic waste disposal and/or treatment.

[0113] As illustrated schematically in FIG. 7, the alcohol intermediateis vaporized in a nitrogen carrier gas and passed over a fixeddehydrogenation catalyst bed comprising a metallic Cu catalyst.Dehydrogenation reaction product gas is cooled to condense3,3-dimethylbutanal product. The vapor phase exiting the condenserpasses through a mist eliminator to collect entrained condensate whichdrains into a mist liquid receiver/separator. The aqueous phase from theseparator is discharged to aqueous waste treatment and disposal. Theorganic phase comprises the 3,3-dimethylbutanal product. If a high levelof alcohol is present in the organic phase, it may be recycled to thealcohol vaporization step upstream of the fixed bed dehydrogenationreactor. The gas phase passing through the mist eliminator is dischargedto the atmosphere through a flare. The organic phase may be recycled asdiscussed above, or used in the synthesis of neotame, optionally afterpurification as a preliminary step in the neotame process.

[0114]FIG. 9 illustrates further detail of a preferred process of theinvention for the continuous conversion of 3,3-dimethylbutanol to3,3-dimethylbutanal. Liquid 3,3-dimethylbutanol containing 0.1% to about7.0% by weight water is transferred continuously from an alcohol storagetank 101 by a pump 103 to a gas fired furnace 105 where it is vaporized.An inert diluent gas, preferably nitrogen, is transferred underautogenous pressure from a liquid nitrogen storage bottle 107 throughfurnace 105 where it is heated to a temperature between about 250° andabout 400° C. Nitrogen and 3,3-dimethylbutanol vapor are mixed in-lineto provide a dehydrogenation feed gas containing between about 0.1 mole% and about 10 mole % 3,3-dimethylbutanol. The feed gas is introducedcontinuously at a temperature between about 250° and about 400° C. and atotal pressure of between atmospheric and about 30 psig into one of apair of parallel tubular reactors 109 and 111 for dehydrogenation of3,3-dimethylbutanol to 3,3-dimethylbutanal. Feed is switched between thetwo reactors so that only one is ordinarily in operation at anyparticular time, but at least one is in operation essentially at alltimes. Each of reactors 109 and 111 comprises a fixed catalyst bed,respectively designated 113 and 115. Each reactor is in the form of ashell and tube heat exchanger. Each tube is packed with catalyst and thecatalyst in each tube thus comprises a component catalyst bed, thecombination of the component catalyst beds constituting the fixedcatalyst bed of the reactor. Gas is distributed among the tubes andflows through each tube over the component bed contained therein fordehydrogenation of 3,3-dimethylbutanol to 3,3-dimethylbutanal. The tubesare maintained at the desired reaction temperature by transfer of heatfrom a heat transfer medium, typically molten salt, that is circulatedthrough the shell side of the exchanger.

[0115] The catalyst in tubes comprises a metallic copper catalystsupported on an inert support such as silica, alumina or mixturesthereof. The catalyst bodies of which catalyst beds 113 and 115 arecomprised have an average principal dimension between about 0.5 andabout 10 mm, preferably about 2 to about 5 mm, and a B.E.T. surface areabetween about 20 and about 100 m³/g. During operation of reactor 109,the feed gas containing between about 5% and about 20% by volume3,3-dimethylbutanol is introduced continuously into the reactor at atemperature between about 250° and about 375° C. and a total pressure ofbetween about 10 and about 100 psig (69 to about 690 kPa) through aninlet 117 which is in fluid flow communication with 3,3-dimethylbutanolstorage and nitrogen storage via the transfer lines passing throughfurnace 105. When the activity of the catalyst in bed 111 of reactor 109has declined below a desired value, the feed gas is switched to inlet119 of reactor 111 and reaction continued by passage of reacting gasesover catalyst bed 115 while the activity of catalyst bed 113 is beingrestored by regeneration or replacement of the catalyst containedtherein. Regeneration may be accomplished by circulation of heated airthrough the catalyst bed via a catalyst regeneration system ofconventional configuration (not shown in the drawing). Operation ofreactor 111 is carried out under essentially the same conditions asdescribed for reactor 109. Thus, the two catalyst beds are alternated sothat at any time one reactor is in reaction mode and the other inreactivation mode, and the dehydrogenation process may be conducted overan extended period of operation essentially without interruption.Catalyst is supplied from a source 121 and spent catalyst is dischargedto a spent catalyst drum 123.

[0116] Conversion of 3,3-dimethylbutanol to 3,3-dimethylbutanal inreactor 107 or 109 is between about 50% and about 100%.

[0117] Reaction product gas is cooled in a water-cooled condenser 125that is in fluid flow communication with the exit of reactor 109 or 111,and further cooled in a refrigerant cooled condenser 127 incommunication with the exit of condenser 125. Mixed gas and liquidexiting condenser 127 is passed to a gas/liquid separator 129. The gasphase exiting the top of the separator passes through a mist eliminator131 and thence to an off gas flare. Liquid exiting the bottom ofseparator 129 flows to a liquid/liquid separator 133, where the liquidseparates into a lower aqueous phase containing not more than about 1%3,3-dimethylbutanal and not more than about 6% 3,3-dimethylbutanol, andan upper organic phase comprising at least about 85%, preferably betweenabout 89% and about 99%, by weight 3,3-dimethylbutanal, and not morethan about 50%, preferably between about less than 1% and about 20%, byweight 3,3-dimethylbutanol. The 3,3-dimethylbutanal layer is transferredto a crude aldehyde storage tank 135 for use in a reductive alkylationreaction for the manufacture of Neotame. The aqueous layer istransferred to aqueous waste treatment and disposal.

[0118] If desired, the crude aldehyde layer obtained from separator 133may be further processed in a conventional manner known to the art,e.g., by distillation, extraction, or crystallization, to obtain a3,3-dimethylbutanal product of any desired quality or purity.

[0119] An alternative embodiment of the process for dehydrogenation of3,3-dimethylbutanol is illustrated in FIG. 10. Supply of alcohol fromstorage tank 201, supply of nitrogen from bottle 207, preheating ofalcohol and nitrogen in furnace 205 and mixing of alcohol and nitrogento provide a reactor feed mixture are carried out in a manner identicalto that of the corresponding operations of the process of FIG. 9 asdescribed hereinabove. The feed gas is introduced into dehydrogenationreactor 209 containing a fixed bed 213 comprising a catalyst of the typeused in reactors 109 and 111 of FIG. 9. Fixed bed 213 is divided intothree stages 213 a, 213 b, and 213 c. Reaction gas flows downwardlythrough these stages from reactor inlet 217 to reactor outlet 219,effecting a significant initial conversion of 3,3-dimethylbutanol to3,3-dimethylbutanal. Due to the endothermic nature of the reaction, thereaction gas temperature declines in its passage through each of stages213 a, 213 b, and 213 c. In order to restore the gas temperatureentering each stage to a temperature to the desired range, heated inertgas is introduced into the reaction gas stream in a chamber 214 abetween catalyst stages 213 a and 213 b, and a chamber 214 b betweencatalyst stages 213 b and 213 c. This is accomplished by dividing thenitrogen stream exiting furnace 205 into three streams, the first ofwhich is mixed with 3,3-dimethylbutanol vapor upstream of inlet 217, thesecond of which is introduced into the chamber 214 a, and third of whichis introduced into chamber 214 b. Chambers 214 a and 214 b may be void,or comprise inert packing.

[0120] To provide control of gas temperature entering each of thecatalyst stages, cool nitrogen gas by-passed around furnace 205 may beinjected into the dehydrogenation feed stream entering the reactor, orinto the inert heating gas introduced between stages, in each instanceat a rate regulated to control temperature in response to measurementmade by sensors (not shown) at each of these points.

[0121] The remainder of the operation of the process of FIG. 10 isessentially identical to the operation of the corresponding portions ofthe process of FIG. 9.

[0122] In a further alternative embodiment, a single tube tubularreactor may be banded with electrical heaters to establish and maintaindesired temperatures in a plurality of catalyst subregionslongitudinally sequenced within the catalyst bed. In such a system, thecatalyst bed may be diluted with inert packing to facilitate control ofthe reaction, control of temperature within each of the sequentialsubregion, and tailoring the reaction temperature to the composition ofthe reaction mixture as it flows from subregion to subregion. Accordingto a still further alternative, a tubular reactor may be divided into aplurality of segments in series, with a sand bath positioned betweeneach successive pair of segments for reheating the reacting gasesexiting the upstream segment to a temperature appropriate forintroduction into the downstream segment.

[0123] Beyond its utility in the preparation of[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine, 1-methyl ester,3,3-dimethylbutanal is useful as an intermediate in the preparation ofother sweetener products such as[N-(3,3-dimethylbutyl)-L-α-aspartyl-α-methyl-L-tyrosine 1-methyl ester(EP 0 866 073), aspartyl dipeptide amide derivatives (EP 0 818 463) andthe aspartyl tripeptide derivatives (JP09278792), N-alkylaspartyldipeptides (JP09227589), and other stable aspartylamide sweeteners (EP 0784 050). It has further utility in the preparation of a wide variety ofpharmaceutical products including, e.g., various substituted 2-pyranonesuseful as HIV protease inhibitors (U.S. Pat. No. 5,808,062), substitutedpeptides useful as calcium channel blockers (WO98/10838), ureaderivatives useful as raf kinase inhibitors WO98/52559), aryl ureasuseful as p38 kinase inhibitors (WO98/52558), and aminediol-containingpeptide analogs as retroviral protease inhibitors (Frost et al.,Tetrahedron Letters, 37(51), pp. 9139-9142), erythromycin derivatives(EP 0 614 905).

[0124] The following examples illustrate the invention.

EXAMPLE 1

[0125] Sulfuric acid (10 g; 98 mmol; 96% by weight) and heptane (10.2mL) were charged to a glass liner. The glass liner was placed into ajacketed autoclave and the head attached. After the system was flushedwith nitrogen, the charge mixture was cooled to −14° C. under agitationat 400 rpm. At this temperature, ethylene was introduced into the headspace of the autoclave at a pressure of 120 psig, and this pressure wasmaintained throughout the course of the ensuing reaction. Once ethylenepressure had been applied, addition of isobutylene was commenced at ametered rate of 1 mL/hr (0.59 g/hr) while the reaction mixture wasmaintained at −14° to −16° C. by removal of heat to cooling fluid(ethylene glycol) in the jacket. Addition of isobutylene was terminatedafter four hours, during which the total amount of isobutylene added was2.36 g (42 mmol). The autoclave was then vented to remove ethylene fromthe head space, with 0.31 g ethylene remaining in heptane solution afterventing (solubility of ethylene in heptane at −14° C. and 40 psig isabout 1.1 mol.=/L).

[0126] After ethylene was vented, the glass liner was removed from theautoclave. The condensed phase reaction mixture comprised two liquidlayers. The upper layer (7.6 g) was a water white liquid while thebottom layer (12.7 g) was a viscous yellow oil. The two layers wereseparated, after which water (6 g total) was added dropwise withstirring to the separated bottom layer, resulting an exotherm to about85° C., reflecting hydrolysis of 3,3-dimethylbutyl hydrogen sulfate,di(3,3-dimethylbutyl) sulfate, and any 3,3-dimethylbutyl ethyl sulfateto 3,3-dimethylbutanol, and a further phase separation. The top layerobtained in this further separation was a dark red oil (5.1 g) and thebottom layer was a light yellow solution (12.68 g). The top layer wasanalyzed by GC and found to contain a total of 1.31 g (m.w.=102; 12.8mmol) crude 3,3-dimethylbutanol (30.4% based on isobutylene added and13% based on sulfuric acid). Purification of the alcohol could beachieved by NaOH neutralization of the top layer obtained in thehydrolysis reaction followed by distillation at 85 to 90 mm Hg and about92° C.

[0127] Based on the results of this example, it appeared reasonable toobtain 3,3-dimethylbutanol yields of 30-50% based on isobutylene, 12.5to 21% (higher if higher conversions are achieved) based on sulfuricacid, and an ethylene yield equal to that achieved on isobutylene. A 90%recycle of heptane is possible. Sulfuric acid cannot be recycled unlesssubjected to spent acid recovery and concentration.

EXAMPLE 2

[0128] Each of a series of alkylation/esterification and hydrolysisreactions was carried out substantially in the manner described inExample 1. Sulfuric acid (96% by weight) and heptane were added to aglass liner. The system was flushed with nitrogen and the charge mixturecooled to −15° to −20° C. under agitation at a stir rate of 800 rpm.After the mixture was cooled, ethylene pressure was applied andmaintained at a constant level. Uptake of ethylene during the subsequentreaction was monitored. After ethylene pressure had been applied, ametered addition of isobutylene was initiated. After isobutyleneaddition was complete, the autoclave was vented for removal of ethylene.

[0129] The glass liner was thereafter removed from the autoclave. Aftereach reaction, the content of the glass liner was observed to containtwo layers, a water white top layer and a viscous yellow oil on thebottom. The top layer was removed, after which the bottom layer wasintroduced into a distillation pot along with 2× its volume of water.Under nitrogen, the distillation pot was heated to 125° C. and overheadcondensate fractions were collected at 90° and 100° C. In each instance,two layers were observed in the collection flask. The top layer wasanalyzed by G. C. to determine the amount of recovered3,3-dimethylbutanol. The reaction conditions, gross yield of3,3-dimethylbutanol, and yields on raw materials for the severalreactions of this Example are set forth in Table 1.

[0130] As used in this table and elsewhere in these examples, “3-3 DMB”shall mean “3,3-dimethylbutyl,” “3,3-dimethylbutyr-,” or“3,3-dimethylbutyric,” depending on context. Where “DMB ester(s)”appears, the reference is to esters of sulfuric acid, eitherdi(3,3-dimethylbutyl) sulfate, 3,3-dimethylbutyl hydrogen sulfate,3,3-dimethylbutyl ethyl sulfate or 3,3-dimethylbutyl t-butyl sulfate, orsome mixture of two or more of these. TABLE 1 mmol % vs. % vs. SulfuricEthylene Isobutylene 3,3-DMB % vs. Ethylene ethylene % vs. Acid Heptane(mL) (psig) (mL/min) Rxn time alcohol Isobutylene (rxn) total H₂SO₄ 1010 120 0.017 4 21 48.9 30.0 16.0 20.6 10 20 100 0.017 4 23 53.5 34.618.8 22.5 10 20 120 0.034 2 25 58.2 33.3 17.2 24.5 10 10 120 0.051 1.521 43.4 51.2 20.4 20.6 10 20 80 0.034 2 24 55.8 50.3 24.4 23.5 10 10 1200.034 3 34 52.7 47.5 25.1 33.3 10 10 80 0.034 3 27 41.9 39.4 26.6 26.520 10 80 0.034 4 37 43.0 29.3 23.8 18.1 10 10 120 0.034 4 40 46.5 37.119.2 39.2 20 10 120 0.051 3 32 33.1 35.9 25.7 15.7 10 10 120 0.034 223.5 54.7 46.0 20.2 23.0 20 20 120 0.068 3 81 62.8 45.2 35.0 39.7 10 10100 0.034 3 29.5 45.8 39.7 22.3 28.9 10 10 140 0.034 3 30.5 47.3 40.318.0 29.9

[0131] Note that ethylene usage includes ethylene consumed in thereaction, ethylene contained in the head space, and ethylene absorbedinto the heptane phase. Set forth in FIG. 1 is a plot of gross3,3-dimethylbutanol yield, as well as yields on isobutylene, ethylene,and sulfuric acid, as a function of addition time for an initial chargeof 10 g sulfuric acid and 10 mL heptane, an ethylene pressure of 120psig, and an isobutylene addition rate of 0.034 mL/min. Note that yieldson ethylene and isobutylene reach a maximum and then decrease,indicating a loss in selectivity as higher amounts of total olefin areadded relative to the sulfuric acid charge, i.e., as the sulfuric acidbecomes relatively dilute due to consumption of HSO₄ ⁻ during the courseof the reaction.

[0132] Set forth in FIG. 2 is a plot of 3,3-dimethylbutanol produced asa function of ethylene pressure under the conditions otherwise the sameas those of FIG. 1, and yields obtained on isobutylene, ethylene(reacted), ethylene (total), and sulfuric acid. A plot of ethyleneuptake vs. time at various levels of ethylene pressure is set forth FIG.3. Optimal results for the runs of this example were obtained with asulfuric acid charge of 10 g, a heptane charge of 10 mL, an ethylenepressure of 120 psig, and an isobutylene feed rate of 0.068 mL/hr.

EXAMPLE 3

[0133] Sulfuric acid (20 g; 196 mmol; 96% by weight) and heptane (20 mL;13.45 g) were charged to a glass liner for a 100 cc Parr autoclave. Theglass liner was placed into the autoclave and the head attached. Theautoclave was jacketed and provided with an overhead magnetically drivenstirrer, a thermocouple, a gas inlet for nitrogen and an inlet forisobutylene. Cooling was provided by circulation of an ethyleneglycol/water solution through the jacket from an insulated bath. Afterthe system was flushed with nitrogen, the charge mixture was cooled to−15° C. under agitation at 800 rpm. At this temperature, ethylene wasintroduced from a reservoir into the head space of the autoclave at apressure of 120 psig, and this pressure was maintained throughout thecourse of the reaction. Twenty five minutes after ethylene pressure wasapplied, addition of isobutylene was commenced at a metered rate of 8.16mL/hr (4.81 g/hr) while the reaction mixture was maintained at −15° C.by removal of heat to cooling water in the jacket. After 50 minutes, theaddition of isobutylene was terminated, at which point the cumulativeamount of isobutylene added was 4 g (72 mmol); and 15 minutes aftertermination of isobutylene addition, the autoclave was vented. Uptake ofethylene was measured by the drop in pressure in the reservoir (of knownvolume). Under the conditions of this example, the initial uptake ofethylene was 2.46 g (88 mmol; 0.123 g/mL) heptane; and uptake ofethylene during the reaction was determined to be 2.13 g (76 mmol), sothat total ethylene consumed and vented was 4.59 g (160 mmol).

[0134] After ethylene was vented, the glass liner was removed from theautoclave. It was observed that the reaction mixture comprised twoliquid layers. The top layer was removed as a light yellow liquid (13.61g), leaving a viscous yellow bottom layer. A GC analysis of the toplayer gave about 1.7% by weight impurities (0.23 g) total. Proton NMRanalysis of the bottom layer in DMSO-d₆ indicated roughly the followingcalculated quantities:

[0135] R—CH₂—SO₃—X (X═H or R′ where R¹ is ethyl or 3,3′-dimethylbutyland R is methyl or t-butyl-CH₂): 66 mmol (of which roughly 80% was3,3-dimethylbutyl-OSO₃X and the remainder Et-OSO₃X)

[0136] ethers (R—CH₂—O—CH₂—R): 3 mmol; R and R¹¹ are independentlymethyl or t-butylCH₂

[0137] heptane: 0.2 to 0.3 g

[0138] Calculated isobutylene usage was 3.3 g (59 mmol) (assumes allether as bis(3,3-dimethylbutyl) ether). Calculated ethylene usage was2.02 g. (72 mmol).

EXAMPLE 4

[0139] Sulfuric acid (5 g; 66% by weight; 49 mmol) and heptane (6.73 g;67 mmol) were charged to a glass liner for an autoclave of the typegenerally described in Example 3. The autoclave was further providedwith an inlet for sulfuric acid. The glass liner was placed in theautoclave and the head attached. After the system was flushed withnitrogen, the charge mixture was agitated at a stir rate of 800 rpm andcooled to −15 degrees C. At this temperature, ethylene was added at anoverhead pressure of 120 psig and this pressure was maintainedthroughout the course of the subsequent alkylation/esterificationreaction. Fifteen minutes after ethylene pressure was applied from areservoir, a metered addition of isobutylene was initiated at a rate of3.06 mL/hr (density of isobutylene=0.59; 1.81 g/hr; 31 mmol/hr) and ametered addition of sulfuric acid (96% by weight) was initiated at arate of 3.32 g/hr (32.5 mmol/hr) while the reaction temperature wasmaintained at −15 degrees C. After 4.5 hr of simultaneous addition, theintroduction of both the isobutylene and sulfuric was terminated. Totalsulfuric acid addition was 19.95 g (196 mmol); total isobutyleneaddition was 13.77 mL (145 mmol). Upon termination of acid andisobutylene addition, the head pressure of ethylene was vented. Uptakeof ethylene was measured by the drop in pressure of the ethylenereservoir (of known volume). Under the conditions of this example, theinitial uptake of ethylene was 66 mmol (1.85 g) and uptake during thereaction was 1.26 mmol (3.53 g), for a total uptake of 192 mmol (5.38g).

[0140] The glass liner was removed from the reactor. It contained twoliquid layers. The top layer was removed as a light yellow liquid (8.87g; 2.14 g weight gain based on the heptane charge) while the bottomlayer was a viscous yellow oil (27.86 g; 7.91 g weight gain based onacid charge).

[0141] Proton NMR analysis of the bottom layer in DMSO-d₆ indicated 2 byintegration roughly 80 mmol eq. of alkylsulfate groups of which themajority appeared to be 3,3-dimethylbutyl sulfate groups. Yield onisobutylene (145 mmol charge) was 55%; yield on ethylene (192 mmolconsumption) was 42% and yield on sulfuric acid (195 mmol charge) was41%.

EXAMPLE 5

[0142] Additional alkylation/esterification reaction runs were madesubstantially in the manner described in Example 4 but with variation inthe combination of initial heptane charge, total sulfuric acid charge,isobutylene addition rate, ethylene pressure and total reaction time.Total 3,3-dimethylbutanol yield and percentage yield on sulfuric acid,ethylene, and isobutylene are set forth in Table 2. TABLE 2 AdditionalExamples Using Method B for Alkylsulfate Synthesis 3,3-DMB Heptane H₂SO₄C₂H₄ C₄H₈ total rxn esters Rxn# (mL) (g) psig mL/min time(hr) meq %H₂SO₄ % C₂H₄ % C₄H₈ 21 20 20.53 120 0.068 3 80 40 36 62.5 22 10 21.56120 0.068 3 97 46 53 76 23 20 12.65 120 0.034 2.5 41 27 23 64 24 1019.95 120 0.051 4.5 80 41 42 55 25 0 21.37 120 0.051 4.5 58 28 41 40 260 17.08 140 0.041 4.5 52 31 37 44 27 0 24.82 140 0.031 4.5 62 26 41 43

EXAMPLE 6

[0143] Further alkylation/esterification reaction runs were conductedsubstantially in the manner described in Example 4 except that: in tworuns the sulfuric acid and isobutylene additions were each completedafter three hours; in the third run, sulfuric acid addition andisobutylene addition were carried out over five hours; in two runs, thereaction temperature was −14° C.; and in another run the reactiontemperature was −11° C. The results of the runs of this example are setforth in Table 3. TABLE 3 Additional Examples Using Method B forAlkylsulfate Synthesis (3 hr addition of isobutylene and sulfuric at ca.−14° C. with 10 mL Heptane and 120 psig ethylene) meq. 3,3-DMB Run #esters % Isobutylene % Ethylene % H₂SO₄ 30  80 62 45 40.5 31  89 59 4545   32 110 62 48 40.5

EXAMPLE 7

[0144] Sulfuric acid (5 g; 66% by weight; 49 mmol) and heptane (6.65 g;66.5 mmol) were charged to a glass liner for an autoclave of the typeused in Example 4. The glass liner was placed in the autoclave and thehead attached. After the system was flushed with nitrogen, the chargemixture was agitated at a stir rate of 800 rpm and cooled to −15 degreesC. At this temperature, an overhead pressure of 120 psig ethylene wasestablished and maintained throughout the course of the reaction bydelivery of ethylene from a reservoir. Five minutes after ethylenepressure was initially applied, metered addition of isobutylene wascommenced at a rate of 3.36 mL/hr (1.98 g/hr) and metered addition ofsulfuric acid simultaneously initiated at a rate of 4.95 g/hr (49mmol/hr). During addition of acid and isobutylene the temperature wasmaintained at −15 degrees C. by circulation of ethylene/glycol watersolution through the autoclave jacket. After three hours of simultaneousaddition of sulfuric acid and isobutylene, sulfuric acid addition wasterminated (total sulfuric acid addition=19.85 g; 194 mmol). Isobutyleneaddition was continued for an additional three hours at a rate which wascontinuously decreased in a linear fashion from 3.36 mL/hr when sulfuricacid addition was terminated to 0.84 mL/hr just before termination ofisobutylene addition. Total addition of isobutylene was 16.39 mL (173mmol). Upon termination of isobutylene addition, ethylene head pressurewas vented. Under the conditions of this example, initial ethyleneuptake was 65 mmol (1.82 g), and uptake during the course of thereaction was 178 mmol (4.98 g), so that total ethylene consumption was243 mmol (6.80 g).

[0145] The glass liner was removed from the reactor and found to containtwo liquid layers. The top layer was decanted as a light yellow liquid(7.74 g; 1.19 g weight gain based on heptane charge). The bottom layerwas a viscous yellow oil (30.70 g; 10.85 g weight gain based on sulfuricacid charge).

[0146] Proton NMR analysis of the bottom layer in DMSO-d₆ using tolueneas a standard (0.1064 g acid layer; 0.1054 g toluene in mL solvent)indicated by integration that the yield was 76 mmol monoalkyl sulfate,21 mmol dialkyl sulfate, and 7 mmol alcohol. An aliquot of the acidlayer was titrated to determine residual acidity. A sample of the acidlayer (111 g) was weighed into a 125 mL Erlenmeyer flask. To this samplewas added 0.100N NaOH (25.0 mL) and methyl red as an indicator. Thesample was back titrated against a 0.100N aq. HCl (15.9 mL) giving 8.2mmol [H⁺]/g acid layer.

[0147] A second aliquot of the acid layer was analyzed by ionchromatography which indicated a 3,3-dimethylbutyl sulfate to ethylsulfate ratio of 1.0:0.099 (91% 3,3-dimethylbutyl groups). Using thisarea ratio to factor the quantity of 3,3-dimethylbutyl groups in thesulfate ester formation determined via NMR analysis, 114 mmol3,3-dimethylbutyl equivalents were calculated. The quantity of remainingunreacted sulfuric acid was determined to be 36.8% on a weight basis(11.3 g; 115 mmol; 41% H₂SO₄ reacted). Based on the above analysis theyield on isobutylene (173 mmol) was 66%; yield on ethylene (243 mmol)was 47%; and yield on sulfuric acid (194 mmol) was 59%.

EXAMPLE 8

[0148] Additional alkylation/esterification reaction runs were conductedsubstantially in the manner described in Example 7, but with variationsin the total sulfuric acid charge, rate of sulfuric acid addition,schedule of isobutylene addition rates, and total isobutylene charge.The results of the runs of this Example are set forth in Table 4. TABLE4 Reaction # 40 41 42 43 Total H2SO4 199 196 197 194 (mmol) Rate H₂SO₄50-3 hr 75-2 hr 50-3 hr 48-3 hr (mmol/hr) Initial Rate 35.4-3 hr 35.4-3hr 35.4-3 hr 35.4-3 hr Isobutylene (mmol/hr) Final rate 17.7-3.5 hr17.7-2 hr ramp to ramp to (mmol/hr) 0-2 hr 9-3 hr Total 168 145 144 173Isobutylene (mmol) Total 226 213 235 242 ethylene (mmol) mmol di- 1611.5 19.5 21 alkylsufate (NMR) mmol mono- 68 66 71 76 alkylsulfate (NMR)mmol free 9 6 3 7 alcohol ratio 1:0.074 1:0.283 1:0.214 1:0.099 3,3DMB:ethyl (I.C.) total 101 74 93 114 3,3-DMB esters meq. & yield on 51 38 4759 H₂SO₄ % yield on 47 35 40 47 ethylene % yield on 60 51 65 66isobutylene [H+]/ — 9.7 9.05 8.2 g (titration)

EXAMPLE 9

[0149] Sulfuric acid (20 g; 66% by weight; 196 mmol) and heptane (20 mL;13.45 g) were charged to a glass liner for an autoclave of the type usedin Example 4. The glass liner was placed in the autoclave and the headattached. After the system was flushed with nitrogen, the charge mixturewas agitated at a stir rate of 800 rpm and cooled to −15 degrees C. Atthis temperature, an overhead pressure of 120 psig ethylene wasestablished and maintained throughout the course of the reaction bydelivery of ethylene from a reservoir. Twenty five minutes afterethylene pressure was initially applied, metered addition of isobutylenewas commenced at a rate of 8.16 mL/hr (4.81 g/hr). During addition ofisobutylene the temperature was maintained at −15 degrees C. bycirculation of ethylene/glycol water solution through the autoclavejacket. The addition of isobutylene was terminated after 50 minutes(total isobutylene added 4 g; 72 mmol). The ethylene head pressure wasvented 15 minutes after termination of isobutylene addition. Under theconditions of this example, initial ethylene uptake was 88 mmol (2.46 g;0.123 g/mL heptane), uptake during the course of the reaction was 76mmol (2.13 g), so that total ethylene consumption was 160 mmol (4.59 g).

[0150] The glass liner was removed from the autoclave and observed tocontain two liquid layers. The top layer was removed as a light yellowliquid (13.16 g; GC analysis gave about 1.7% by weight impurities; 0.23g total), while the bottom layer was a viscous yellow oil (25.24 g).Proton NMR analysis of the bottom layer in DMSO-d₆ indicated roughly thefollowing calculated quantities: 66 mmol R—CH₂O—SO₃—X groups (X=H or R′)of which 80% (roughly) are 3,3-dimethylbutyl-OSO₃—X and the remainderEt-OSO₃—X and 3 mmol alcohols (R—CH₂OH).

[0151] Water (25.1 g) was added to the bottom layer, and the reactionmixture was distilled under nitrogen (no column). A light fraction wascollected at 70°-90° C. (0.3 g; which by area % contained 0.25 g heptaneand 0.04 g 3,3-dimethylbutanol) and a second fraction at 90° to 98° C.Condensation of the second fraction produced a two phase condensatecomprising an organic top layer (5.1 g) and an aqueous bottom layer (6.1g). The top layer of the second fraction condensate containedbis-(3,3-dimethylbutyl)ether (0.352 g), ethanol (0.2 g) and heptane (0.1g). The aqueous layer contained ethanol (0.25 g) and a small amount of3,3-dimethylbutyl alcohol. Water (14 g) was then added to thedistillation pot and distillation resumed. A third fraction wascollected at 980 ° to 100° C. which contained two layers. The toporganic layer (0.7 g) was analyzed and determined to contain3,3-dimethylbutanol (0.36 g), and the remainder, by area, higher boilingimpurities. The bottom aqueous layer (13.34 g) contained only a trace ofalcohols. A summary of the compositions of the fractions obtained in thereactive distillation, and the temperatures at which they were obtained,is set forth in Table 5. TABLE 5 Distillation Pot Fraction #1 Fraction#2 Fraction #3 Total Temperature 125° C. 70°-90° C. 90°-98° C. 98°-100°C. — 3,3-DMB alcohol — 0.04 g 4.42 g  0.36 g  4.82 g Heptane — 0.25 g 0.1 g —  0.35 g 3,3-DMB ether — — 0.32 g —  0.32 g Ethanol — trace  0.2g —  0.2 g Aqueous 38.2 g —  6.1 g* 13.34 g 57.64 g Total wt (org/aq.)trace oil/38.2 g  0.3 g 5.1/ 0.7/ 6.1/  6.1 g 13.34 g 57.64 g

[0152] Total weight of the charge to the reactive distillation was 63.34g (25.24 g alkylation/esterification reaction product and 39.1 g water).Of this 63.74 g were accounted for in the fractions obtained.

[0153] The heptane layer obtained in the reaction of Example 3 wassubjected to a simple takeover distillation at bath temperature of 125°C. Collection was continued until the pot temperature reached 100° C.,at which point 10.9 g distillate had been recovered from an initialcharge to the pot of 12.47 g. GC analysis of the distillate indicated0.15% by weight impurities and the remainder heptane (10.73 g). Heptanebalance was as follows:

[0154] Heptane in=13.45 g

[0155] Heptane from distillation of alk./ester. acid layer=0.35 g

[0156] Heptane in org. layer of alk./ester=13.61-0.23=13.38 g

[0157] Accountability prior to distillation=102%

[0158] Distillation gave 10.73 g heptane=80% recovery overall

[0159] Yields of 3,3-dimethylbutanol obtained from the distillation, andyields on raw materials initially charged are set forth in Table 6.TABLE 6 grams mmol % % % 3,3- 3,3- yield on yield on yield on DMB DMB %yield on total rxn sulfuric alcohol alcohol isobutylene ethyleneethylene acid total 4.82 47 65% 30% 62% 24% fractions fraction 2 4.42 4360% 27% 57% 22%

[0160] Fraction #2 material (4.97 g) from the crude takeoverdistillation was refined by distillation at 80 torr and a pottemperature of 125° C. Conditions of the distillation and compositionsof the fractions obtained are set forth in Table 7. TABLE 7 pot fraction#1 fraction #2 total Temperature 125° C. <82° C. 82-84° C. 3,3-DMBalcohol 0.13 g 0.33 g 3.2 g 3.66 g 3,3-DMB ether — 0.15 g 0.15 g Ethanol0.14 — 0.14 g heptane 0.07 g — 0.07 g total 0.26 g 0.9 g 3.36 g 4.52 g(includes water)

EXAMPLE 10

[0161] A simulated 3,3-dimethylbutyl sulfate hydrolysis reaction mixturewas prepared by mixing heptane (5 g), 3,3-dimethylbutanol (5 g), water(10 g), ethanol (5 g), and sulfuric acid (100% basis; 5 g). The chargewas stirred to provide a uniform mixture, and the mixture thereafterallowed to separate. Two layers were obtained, the top layer weighing11.93 g and the bottom layer 18.3 g. Analysis of the top layer indicatedthat it contained 3,3-dimethylbutanol (4.42 g), ethanol (1.65 g),heptane (5.15 g) and water/sulfuric acid (0.7 g by difference). The toplayer was distilled to provide three fractions. Condensing the firstfraction yielded two liquid layers (5.9 g total) together containing 4.1g heptane, with only a trace of either 3,3-dimethylbutanol or ethanol.The second fraction (0.9 g) contained all components, while the thirdfraction (2.3 g) contained 3,3-dimethylbutanol and a small amount of anunknown side product. The residue in the pot (2.8 g) contained a smallamount of 3,3-dimethylbutanol and a major fraction of by-product,surmised to comprise bis(3,3-dimethylbutyl) ether.

[0162] It was observed that the residual acid in the organic layerobtained from the initial separation was detrimental to the distillationthereof. A second mixture was made as described above; but, prior todistillation, 0.1 N KOH was added to the mixture to neutralize residualacid (3.5 mmol KOH was required as determined by methyl red indicator).Distillation was carried out at about 100 torr, yielding two majorfractions. The first fraction contained heptane (4.4 g) and a trace of3,3-dimethylbutanol. The second fraction contained 3,3-dimethylbutanol;while the pot fraction contained 0.5 g alcohol with only a trace ofdecomposition products.

EXAMPLE 11

[0163] A 300 mL ACE pressure rated glass reactor (flask 1) was equippedwith a Teflon coated magnetic stir bar and a thermocouple connected to atemperature controller. Sulfuric acid (98% by weight; 22.8 mL; 41.9 g;0.428 mmol) and heptane (30 mL) were added to flask 1. The flask wascooled to −15° C. with a cooling bath and pressurized to 100 psi withethylene. Heptane (20 mL) and isobutylene (12 g) were added to aseparate ACE 75 mL pressure rated flask (flask 2). Flask 2 waspressurized to 120 psi. The isobutylene/heptane mixture in flask 2 wasadded to flask 1 with vigorous agitation over a period of three hours (arate of 0.2 mL per minute). Flask 1 was maintained at 110 psi ethyleneand −15° C. throughout the reaction. After addition ofisobutylene/heptane solution was complete, agitation of the reactionmixture in flask 1 was continued for another 20 minutes before the flaskwas depressurized and warmed to 0° C. Water (100 mL) was added slowly tothe mixture in flask 1 at 0° C., resulting in the formation of twolayers: a heptane layer and a aqueous sulfate layer. The heptane layerwas discarded and the aqueous sulfate layer was transferred into adistilling set up which consisted of a distilling column, a Dean Starkreceiver and a condenser. The 3,3-dimethylbutanol product was distilledfrom the flask as a water azeotrope while the water layer in the DeanStark receiver was returned continuously to the distilling flask. Ayield of 3,3-dimethylbutanol was 48.9% (based on isobutylene).

EXAMPLE 12

[0164] Alkylation and esterification reactions were carried out in themanner described in Example 11 except that decane was substituted forheptane as the solvent, and the initial charge of decane to flask 1 was50 mL. Reaction conditions and work up were otherwise identical to thosedescribed in Example 11. The yield of 3,3-dimethylbutanol product bydistillation of the pregnant liquor obtained from flask 1 was 74.7%(based on isobutylene).

EXAMPLE 13

[0165] 3,3-Dimethylbutanol (10% by volume) was vaporized into a heliumcarrier and passed over a fixed bed comprising CuO (2 g supported onsilica/aluminum containing alkaline earth oxide). Flow rate of the gasstream was 200 sccm at a bed temperature of 260° C. Initially, astoichiometric oxidation reaction was obtained in which3,3-dimethylbutanol was converted to 3,3-dimethylbutanal. Asstoichiometric oxidation proceeded, the CuO in the bed was progressivelyreduced to Cu⁰, after which conversion of 3,3-dimethylbutanol to3,3-dimethylbutanal continued by non-oxidative catalyticdehydrogenation. Conversion of 3,3-dimethylbutanol to3,3-dimethylbutanal was initially about 55%, declining over twelve hoursto approximately 45%, with a corresponding decline in productivity fromabout 1.5 g aldehyde/g catalyst-hr to about 1.25 g aldehyde/gcatalyst-hr. However, a high selectivity to 3,3-dimethylbutanal wasmaintained throughout the run. A plot of selectivity vs. time is setforth in FIG. 4

[0166] Product of the reaction was passed through an ice trap foraldehyde and alcohol recovery. The clear white water mixture obtainedwas purified by distillation (49.9 g recovered material; 76% yield basedon feed to the fixed bed reactor). Composition of the accumulatedcondensate as indicated by GC was 43.5% 3,3-dimethylbutanal (217 g; 66%based on GC rector data), and 56.5% 3,3-dimethylbutanol (28.2 g; 89%based on GC reactor data). Distillation was carried out at 85 to 90 mmHg using a Snyder column with three levels (bulbs). Analysis of theresulting fractions is set forth in Table 8. TABLE 8 Fraction % of(temp) #1 (45° C.) #2 (46-84° C.) #3 (85-86° C.) pot total recoverygrams 18 2.3 22.6 3 45.9 g 92% (of initial) 3,3-DMB % 99 81 0 0 —aldehyde 3,3-DMB % 1 19 100 86 — alcohol 3,3-DMB % 0 0 0 6 — acid %unknowns 0 0 0 8 — g 3,3-DMB 17.8 1.9 0 0 19.7 g 42.9% aldehyde g3,3-DMB 0.2 0.4 22.6 2.6 25.8 g 56.2% alcohol g 3,3-DMB 0 0 0 0.2  0.2 g 0.4% acid g unknowns 0 0 0 0.2  0.2 g  0.5%

[0167] Very little change in composition was observed during thedistillation as indicated by the recovered amounts of each component.Separation of aldehyde from alcohol was very good (82% of the aldehydein the crude feed to the distillation was recovered in 99% purity).

[0168] Although the conversion of alcohol to aldehyde is reversible, theequilibrium is favorable. At the nominal temperatures at which thisreaction was run over a supported Cu catalyst, i.e., in the range of2500 to 300° C., very high conversion to aldehyde is favored. Forexample, with 5 mole % alcohol in the feed stream, the equilibriumconversion to aldehyde was 96% at 300° C. For the computed heat ofreaction of 17 Kcal/mole, the equilibrium constant doubles for each 20°C. temperature increases. Even at 260° C., the equilibrium conversion isover 80% with a 10 mole % alcohol feed.

[0169] The adiabatic temperature decrease on converting 90+% alcoholfeed (5 mole % alcohol) is about 100° C. Productivity of the reaction isvery high. A conversion of greater than 90% was achieved at a gasresidence time of less than 1 second.

EXAMPLE 14

[0170] A stream of 3,3-dimethylbutanol produced in Example 1 wasconverted to 3,3-dimethylbutanal by stoichiometric oxidation with CuO,followed by anaerobic catalytic dehydrogenation over the Cu⁰ catalystproduced in situ in the stoichiometric oxidation reaction. A tubularreactor was constructed comprising a ½″ diameter inner tube adapted tocontain a fixed catalyst bed, and an outer tube concentric with theinner tube, defining an annular space within which feed gas could flowbefore entry into the inner tube. One end of the outer tube was incommunication with an inlet on the inner tube. The other end of theouter tube was connected to a supply of feed gas for the reaction.Heating means surrounding the outer tube were provided for preheatingthe gas entering the reactor system.

[0171] The inner tube of the reactor was charged with Cu oxide on aparticulate inert support (4 g; 70% CuO) and having a particle size ofbetween about 0.6 mm and about 1.7 mm. A constant flow of helium wasestablished through the annular space and inner tube at a temperature of250° C. and a pressure of 10 psig. Wet 3,3-dimethylbutanol (94-95%3,3-dimethylbutanol; 5-6% water) was vaporized into the helium stream at185° C. to produce a feed gas for the reactor comprised of 5% by volume3,3-dimethylbutanol and 95% by volume helium. Conversion of3,3-dimethylbutanol to 3,3-dimethylbutanal proceeded, initially bystoichiometric oxidation. After about 1 to 2 hours, the reaction changedfrom exothermic to endothermic, as indicated by a decline of about 5° C.in the temperature of the catalyst bed. Appearance of the endothermindicated that the CuO was becoming exhausted. Conversion of3,3-dimethylbutanol to 3,3-dimethylbutanal continued, however, byanaerobic catalytic dehydrogenation over Cu⁰. By application of heat tothe feed gas, the temperature of the reaction was raised to a finaltemperature of 325° C., at which the reaction was allowed to runcontinuously for 48 hours, showing very little loss in activity orselectivity. The reaction product was collected in a Fisher bottlecooled to −7° C.

[0172] A summary of the results of 48 hours continuous reaction is setforth in Table 9. TABLE 9 % 3,3-DMB alcohol purity 95% temperature 325°C. g olefin 0.53 grams cat 4 % Select Olefin 0.45 3,3-DMB alcohol feed0.054 g 3,3-DMB ether 0.42 time 47.13 % Select Ether 0.36 total 3,3-DMBalcohol feed 122.42 g 3,3-DMB ester 0.98 total 3,3-DMB aldehyde 113.61 %Select ester 0.85 % total 92.80 g acid 0.46 Conversion to % Select acid0.40 3,3-DMB aldehyde g ald/g cat/hr 0.60 g 3,3-DMB alcohol 6.07 masstotal 122.08 % total Conversion 95.04 % Selectivity to 97.64 3,3-DMBaldehyde

[0173] Selectivity and conversions obtained in the 48 hour reaction runare shown in FIG. 5, with impurity content of the reaction productplotted in FIG. 6.

EXAMPLE 15

[0174] Dehydrogenation of 3,3-dimethylbutanol was conductedsubstantially in the manner described in Example 14. Operation wascontinued over a period of 142.5 hours. 3,3-Dimethylbutanol was fed tothe reactor at a rate of 2.73 g/hr (26.8 mmol/hr; 10 sccm). The catalystconsisted of 4 g (about 2.5 cc) of a copper catalyst designatedCu0330-XLT. Total flow through the bed was 200 sccm using helium as thediluent. Contact time over the catalyst bed was 1.33 seconds. Productgases were analyzed by on line gas chromatographs. Results of run ofthis example are set forth in Table 10. TABLE 10 Results from 142.5 hrContinuous Dehydrogenation of 3,3-dimethylbutanol Using Cu-0330 XLTCatalyst % isolated Mmol grams wt % recovered recovered recovered basedon fed (G.C.) (G.C.) (G.C.) wt % grams mmol alcohol Fed 3,3-DMB Alcohol3823 389.9 100 3,3-Dimethylbutanal 3543 354.3 91.9 85.3 273 2730 71.4Bis(3,3-DMB) ether 8.5 1.6 0.4 3,3-DME-3,3- 17.6 3.5 0.9dimethylbutyrate 3,3-Dimethylbutyric acid 14.3 1.7 0.4 3.23 10.3 89 2.332,3-dimethyl-2-butene 10 0.8 0.2 and 3,3-dimethyl-1- butene unreacted3,3-DMB 230 23.5 6.1 8.26 26.4 259 6.8 alcohol

[0175] The quantities of products produced were calculated from thecollective sum of all the traces of the on-line gas chromatographs,based on percentage of product vs. 3,3-DMB alcohol fed. The recoveredamount of aldehyde was 320.3 g (7.2 g. calculated hydrogen release); 84%recovery. The high relative amount of 3,3-DMB acid recovered may havebeen partially due to preferential condensation and partially due to airoxidation of aldehyde in storage and transportation.

EXAMPLE 16

[0176] Using a process substantially as described in Example 14, severalcatalysts were evaluated for their effectiveness in the dehydrogenationof 3,3-dimethylbutanol to 3,3-dimethylbutanal. Compositions of thecatalysts are set forth in Table 11, and other characteristics of thecatalysts are set forth in Table 12. TABLE 11 Composition (XRF) ofCommercial Catalysts for Dehydrogenation Cu-0330XLT X-415Tu C3150TRCu-0865XLE Catalyst (Engelhard) (Calsicat) (Degussa) (Engelhard) % Cu37.4 47.8 36.2 43.5 % Si 0 3.1 24.2 10.4 % Al 14.9 11.3 0.1 0.7 % Na 1.23.4 1.4 1.9 % Ca 0 2.1 0 11.7 % Mn 0 0.4 0 0

[0177] TABLE 12 Dehydrogenation Catalyst Physical CharacteristicsCu-0330XLT X-415Tu C3150TR Cu-0865XLE Catalyst (Engelhard) (Calsicat)(Degussa) (Engelhard) Surface area 30 100 50 45 (m²/g) Pore Volume 0.160.3 0.83 0.45 (ml/g) Density (g/mL) 1.63 1.2 0.54 0.74 Crush Strength11.31 20 — 2.94 (lb/mm)

[0178] In these tests, Engelhard catalyst 0330-XLT displayed a catalystlife in excess of 100 hours while maintaining a >90% conversion ofalcohol and >95% selectivity to aldehyde (selectivity approached 98%while conversion dropped below 90% after 128 hours). The decline inconversion became apparent at the 80 hour mark of a 142.5 hour testreaction; but there was no loss of selectivity. Degussa catalyst C3150TRand Englehard Cu-0865XLE also provided generally favorable selectivityand reasonable conversions.

EXAMPLE 17

[0179] Sodium borohydride (1.61 g) was added dropwise with to a solutionof 3,3-dimethylbutyric acid (1.86 g) in DMSO (30 mL) under vigorousagitation at room temperature. Subsequently, a solution ofmethanesulfonic acid (3.6 mL) in DMSO (10 mL) was added to the mixture.The resulting reaction mixture was stirred for another hour, after whichit was quenched with a 10% by weight aqueous sodium hydroxide solution.Yield of 3,3-dimethylbutanol was 50%. The reaction mixture was worked upby repeated extraction with ether, washing the ether extract with water,drying the washed extract by contact with a desiccant, and distillingthe dried extract to remove the ether. The resulting 3,3-dimethylbutanolproduct is a colorless liquid and appears to be pure based on NMR.

EXAMPLE 18

[0180] 1-Chloro-3,3-dimethylbutane (15 g), zinc oxide (6 g) and water(60 g) were charged to a 150 mL Parr reactor. The reactor was sealed andthe charge mixture was heated and stirred at 220° C. for 5 hours.Reactor pressure was about 800 psi. Yield of 3,3-dimethylbutanol was70%.

EXAMPLE 19

[0181] A reactor was charged with potassium acetate (196 g),1-chloro-3,3-dimethylbutane (241 g) and polyethylene glycol (300 MW; 600mL). The mixture was heated to reflux and maintained under refluxconditions for 17 hours, then cooled to 100° C. A solution of KOH (197g) in water (150 mL) was added to the reaction mixture, and theresulting hydrolysis charge mixture was heated to reflux for 2 hours.Distillation and work-up provided 3,3-dimethylbutanol in 81% yield (165g).

EXAMPLE 20

[0182] Lithium aluminum hydride (4.93 g; 0.13 mmol) was added to asolution of ethyl ester of 3,3-dimethylbutyric acid (1.44 g; 0.01 mmol)in dry tetrahydrofuran (20 mL) and the resulting mixture was heated toreflux for 6 hours, then cooled to room temperature. After the reactionmixture was cooled, it was treated carefully with water (20 mL) and thenextracted with diethyl ether (3 times with 30 mL aliquots). Combinedether layers were washed with water and a saturated sodium chloridesolution then dried over sodium sulfate. Evaporation of the solvent gaveessentially pure 3,3-dimethylbutanol in an isolated yield of 77%.

EXAMPLE 21

[0183] A potassium acetate solution was prepared by reaction of KOH andacetic acid in polyethylene glycol (MW=300). After removal of waterformed in the neutralization, 1-chloro-3,3-dimethylbutane was added andthe resulting mixture refluxed for 17 hours with a gradual increase intemperature from 118° to 132° C. at the end of the reaction. Potassiumhydroxide dissolved in water was then added to the reaction mixturewhich was refluxed for two hours. The 3,3-dimethylbutanol was recoveredfrom the reaction mixture by steam distillation. Yield was 81%.

EXAMPLE 22

[0184] Various solvents were tested in preparation of the acetate esterof 3,3-dimethylbutanol by acetoxylation of 1-chloro-3,3-dimethylbutanewith K acetate. Solvents tested were toluene, dimethylformamide, aceticacid, methanol, propylene glycol, and 1-methyl-pyrrolidinone (NMP). Themost favorable results were obtained with NMP.1-Chloro-3,3-dimethylbutane (1.5 g; 12.4 mmol) potassium acetate (13.7mmol; 10% excess) and NMP (5 mL) were placed in a three neck roundbottom flask equipped with reflux condenser, thermometer, and Tefloncoated stirring bar. The suspension was heated to 120° C. and stirred atthat temperature for 22 hours under an inert atmosphere. The reactionmixture was cooled to ambient temperature, the white precipitateobtained from the reaction was removed by filtration, and the liquidphase analyzed by GC-MS, which established the formation of the acetateester of 3,3-dimethylbutanol.

EXAMPLE 23

[0185] 3,3-Dimethylbutyl acetate (2 g; 13.8 mmol), KOH (0.875 g; 15.3mmol), and methanol (10 mL) were introduced into a two neck round bottomflask provided with a reflux condenser, thermometer, and stirring bar.The resulting solution was stirred for two hours at room temperature,during which time the acetate was quantitatively converted to3,3-dimethylbutanol. Only traces of acetate were detected in the GCtrace. Similar results were obtained using 1-methyl-pyrrolidinone (10mL) and water (1 mL) as the solvent medium. Distillation of the alcoholcaused potassium acetate to be reformed in the distillation residue. Theresidue may be recycled for further synthesis of the acetate ester of3,3-dimethylbutanol per the protocol described in Example 22.

EXAMPLE 24

[0186] Ethylene oxide (3 mL; 60 mmol; 2 equival.) was condensed at −5°C. and diluted with dry ether (20 mL). A solution of t-butyl lithium(1.7 M in pentane; 17 mL; 30 mmol; diluted with 40 mL ethyl ether) wasprepared and added dropwise to the ethylene oxide solution at −78° C.The reaction mixture was stirred at −78° C. for another hour after whichit was allowed to warm up to room temperature and quenched with dilutesulfuric acid. The ether layer was decanted and the aqueous layer wasextracted with ether. The combined ether layers were washed with waterand dried with MgSO₄. Solvent removal followed by distillation provideda 48% yield (1.48 g) 3,3-dimethylbutanol.

EXAMPLE 25

[0187] A series of runs was conducted in which 3,3-Dimethylbutene oxide(DMEB) was dissolved in a solvent and charged to an autoclave, acatalyst was slurried in the solution in the autoclave, and hydrogenpressure was applied to effect catalytic hydrogenation of the3,3-dimethylbutene oxide to 3,3-dimethylbutanol. Various combinations ofsolvent, catalyst, temperature, hydrogen pressure, reaction time andstir rate were used in the runs of this example. Results of these runsare set forth in Table 13. TABLE 13 Data on the hydrogenation of3,3-dimethylbutene Oxide to 3,3-dimethylbutan-1-ol-1 Start DMEB TempPress Rate Reaction # Solvent ml Catalyst Weight g ° C. psi RPM TimeConversion Sel** % Solvent Effect 7 8 EtOH 2 RaNi 1.3 100 200 1400 559.4 73.6 9 EtOH 2 RaNi 1.3 100 1000 1400 19 100 63.6 10 THF 2 RaNi 1.3100 300 1400 17 100 60.7 11 THF 2 RaNi 1.3 100 1000 1400 6 94.9 46.3 12MeOH 2 RaNi 1.3 100 200 1400 5 35 73.0 13 MeOH 2 RaNi 1.3 100 1000 14005 81.8 56.4 14 MeOH 2 RaNi 1.3 100 1000 1400 4.5 76.3 76.0 15 MeOAc 2RaNi 1.3 100 1000 1400 6 96.9 69.8 16 Hexane 2 RaNi 2.6 100 300 1400 451.7 69.4 17 Hexane 2 RaNi 1.3 100 1000 1400 17 100 69.5 18 Hexane/ 2RaNi 2.6 100 200 1400 5 82.9 74.3 EtOAc Effect of prolonged Contact w.Catalyst 19 Hexane 2 RaNi 1.3 100 1000 1400 64 100 69.5 20 Hexane 2 RaNi2.6 100 1000 1400 5 100 70.7 Temperature Effect 21 Hexane 2 RaNi 2.6 901000 1400 6 22.2 63.9 22 Hexane 2 RaNi 2.6 100 1000 1400 5 100 70.0 23Hexane 2 RaNi 2.6 120 1000 1400 5 65.2 68.9 24 Hexane 2 RaNi 2.6 1401000 1400 5 100 75.7 25 Hexane 2 RaNi 2.6 150 1000 1400 5 100 76.6 26Hexane 2 RaNi 2.6 160 1000 1400 5 100 75.6 Stirring Effect 27 Hexane 4RaNi 2.6 140 100 400 19 100 42.9* 28 Hexane 2 Ra—Ni 2.6 140 200 400 597.6 53.1 29 Hexane 2 RaNi 2.6 140 200 1600 5 100 78.1 30 Hexane 4 Ra—Ni2.6 160 200 600 5 89.1 57.6 31 Hexane 4 Ra—Ni 2.6 160 200 1600 5 98.470.0 32 Hexane 4 Ra—Ni 2.6 140 400 1000 5 100 74.9 33 Hexane 4 Ra—Ni 2.6140 400 2000 5 100 77.6 34 Hexane 4 Ra—Ni 2.6 140 400 3000 5 100 75.8Pressure Effect 35 Hexane 2 RaNi 2.6 140 200 1600 5 100 78.1 36 Hexane 4Ra—Ni 2.6 140 200 1400 5 100 55.9 37 Hexane 4 Ra—Ni 2.6 140 300 1400 17100 69.0 38 Hexane 4 Ra—Ni 2.6 140 400 1400 17 100 75.7 39 Hexane 4Ra—Ni 2.6 140 600 1400 5 100 75.3 40 Hexane 4 RaNi 2.6 140 1000 1500 5100 66.6 Catalyst Effect 41 Hexane 4 5601* 2.6 140 200 1600 5 100 66.842 Hexane 4 4200* 2.6 140 200 1600 5 100 66.2 43 Hexane 4 2800* 2.6 140200 1600 5 100 74.1 44 Hexane 4 5% Pd/C 0.25 140 200 1600 18 100 43.8 45Hexane 4 5% Pt/C 0.25 140 200 1600 3,3-dimethyl- butane

EXAMPLE 26

[0188] Aluminum chloride catalyst (2.5 g) and pentane (5 mL) werecharged to a 100 mL three neck round bottom flask equipped with aTrubore Stirrer (ACE Glass), gas dispersion tube and thermometer. Themixture was cooled to −40° C. using a dry ice-acetone bath. To the wellstirred catalyst suspension, 2-chloro-2-methylpropene (25 g) was addeddropwise while the temperature was maintained at −40° C. The ethylenewas run through the liquid phase at a rate of 70 mL/min, as controlledby a flowmeter and two bubblers, one at the inlet and the second at theoutlet of the flask. The temperature was kept between −18° and −22° C.The reaction was completed in three hours when the ethylene absorptionslowed significantly (as determined by the flow rates in the front andback bubblers). The liquid product was decanted from the catalyst andtransferred into a separatory funnel, washed with distilled water (5 mL)and dried over CaCl₂ (1 g) for two hours. The yield of1-chloro-3,3-dimethylbutane based on GC analysis was 49%. The two othermajor components were the C₈ chloride (25%) with RT 3.88 minutes andanother unidentified product with RT at 2.88 minutes, likely an isomericC₆ chloride.

EXAMPLE 27

[0189] In a series of alkylation/esterification reactions, sulfateesters of 3,3-dimethylbutanol were produced by reaction of isobutylene,ethylene and sulfuric acid. Sulfuric acid and heptane were charged to a300 mL ACE glass reaction flask which was provided with a Teflon coatedstir bar, and lines for ethylene and isobutylene delivery. The chargewas cooled to −15° C. and placed under constant ethylene pressure. Theisobutylene charge for each run was initially transferred to a graduatedflask separate from the reaction flask, and then delivered to thereaction flask at a substantially constant rate over a period of hoursas the reaction proceeded. During reaction, the temperature wasmaintained at −15° C. using a dry ice-acetone cooling bath. Chargeamounts, charge ratios, periods over which isobutylene addition wasaccomplished, and reaction conditions are set forth Table 14.

[0190] The 3,3-dimethylbutyl sulfate esters produced in the reactionwere hydrolyzed to 3,3-dimethylbutanol. After completion of the reactionin runs NS 109 and NS 112, the acid layer was neutralized with NaOH topH=3, the organic layer was extracted twice with ether, and theremaining aqueous layer refluxed overnight. In runs NS113 and NS115,after isobutylene addition was completed, ethylene pressure was releasedand water was added in small portions while the reaction mass wasmaintained at −15° C. by cooling in the dry-ice acetone bath. In eachhydrolysis run, the alkylation/esterification reaction mixture wastransferred into a two neck round bottom flask and refluxed overnightunder argon. The yields entered in Table 14 are based on GC-MS analysisusing dodecane as the internal standard. No attempt was made to isolatethe alcohol by distillation to determine practical yield of thereaction.

[0191] Exemplary of the runs of this example is run NS114 in whichsulfuric acid (26.3 g; 0.27 mol) and hexane (90 mL) were charged to the300 mL reaction flask. Isobutylene (11 g; 0.196 mol) was initiallytransferred to the separate graduated flask which served as a reservoirfor delivery of isobutylene during the reaction. The reaction flask waspurged twice with ethylene and held open under ethylene line pressure of100 psig. The reactor was immersed in the dry ice-acetone bath which hadbeen precooled to −15 degrees C. The temperature of the reactor wasmonitored by a K type thermocouple inserted into a Teflon coatedthermowell. The isobutylene reservoir was kept under nitrogen pressureof 130 psig. Isobutylene addition was initiated at a rate of 0.05mL/minute while the contents of the reaction flask were stirred at themaximum rate possible. The temperature was maintained at −15 degrees C.throughout the run by addition of dry ice to the cooling bath. Additionof the full isobutylene charge required 5.75 hours. The reaction mixturewas stirred for an additional 30 minutes, after which the ethylenepressure was released and water (100 mL) was added dropwise while thetemperature was maintained at −15 degrees C. Thereafter, the reactionmixture was transferred to the two neck round bottom hydrolysis flaskand refluxed overnight under argon at 85 degrees C. The organic layerwas then separated, the acidic layer was extracted twice with 30 mLaliquots of ether, and the combined organic phases were washed once with10% Na₂CO₃ solution followed by 10% NaCl solution. After the washedorganic layer had been dried over MgSO₄ for three hours, dodecane (5 mL;4.14 g) was added as an internal standard and the mixture was analyzedby GC-MS. The amount of 3,3-dimethylbutanol thus determined was 10.8 gwhich, based on a theoretical of 19.99 g, represented a 54% yield. TABLE14 Run # 141 142 143 144 145 146 Ethylene Pressure 75 90 90 90 100 100Temperature −15 −15 −15 −15 −15 −15 Reactants a. H₂SO₄, mol 0.27 0.220.27 0.27 0.22 0.27 b. C₄, mol 0.196 0.196 0.196 0.196 0.196 0.196 c.solvent, ml 93 50 90 90 90 90 Ratios: a. solvent/H₂SO₄, 6.5 4.3 6.5 6.57.7 6.3 mol/mol b. H₂SO₄/C₄, 1.38 1.12 1.38 1.38 1.12 1.38 mol/mol c.solvent/C₄ 4.9 2.7 4.9 4.9 4.9 4.9 Time of addition C₄ 5 3.5 5 7 7 5.45Hydrolysis Neutralized Neutralized Neutralized 50 ml H₂O 30 ml H₂O 100ml H₂O of the sulfate NaOH, reflux NaOH, reflux NaOH, reflux 80° C.,overnight 80° C., overnight 80° C., overnight 3 hrs at pH = 3.5 3 hrs atpH = 3.5 0.5 hrs at pH = 3.5 Yield, % 18.8 10.3 25 37.2 28.3 54

EXAMPLE 28

[0192] Further alkylation/esterification and hydrolysis reaction runswere conducted substantially in the manner described in Example 27except that the total isobutylene charge, total sulfuric acid charge,ethylene pressure, and time of isobutylene addition in thealkylation/esterification step, and the conditions of the hydrolysisstep, were as set forth in Table 15. In all runs, after the addition ofisobutylene, the ethylene pressure was released and water was added insmall portions at −15 degrees C. The reaction mixture was transferred toa two neck round bottom flask and refluxed overnight under argon at thetemperature indicated in Table 15. Yields were determined by GC-MSanalysis, using dodecane as the internal standard. Further kineticstudies at 90 degrees C. revealed that alcohol formation was practicallycompleted in 3 hours, and that further heat treatment overnight onlyincreased the C₁₂ ether formation up to about 20 area % based on CCanalysis.

[0193] A further run of this example (run 159) was carried out at thesame reactant ratios as run 158. After isobutylene addition, the mixturewas heated to ambient, and the heptane layer was then separated andanalyzed by GC-MS. The amount of C₆ alcohol as determined using dodecaneas the standard was 900 mg (4.5% from the theoretical yield). The acidiclayer was transferred into a distillation setup, water (50 mL) wasadded, and the water-azeotrope was continuously distilled at 102-103degrees C. The water layer was recycled three times and a total of 12.5g organic product was collected. The CC analysis of the crude productshowed C₆-alcohol (64.4 area %) C₁₂-ether (24%), higher boilingunidentified product (4.8%) and ballast heptane. The combined calculatedyield from both layers was 46% crude alcohol. TABLE 15 Run # 150 151 152153 154 155 156 157 158 Ethylene Pressure 100 100 100 100 100 100 115115 115 Temperature −15 −15 −15 −15 −15 −15 −15 −15 −15 Reactants a.H₂SO₄, mol 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.176 0.176 b. C₄, mol0.196 0.196 0.196 0.196 0.196 0.196 0.196 0.13 0.13 C. solvent, ml 90 9090 90 90 90 90 59 59 Ratios: a. solvent/ 6.3 6.3 6.3 6.3 6.3 6.3 6.3 6.36.3 H₂SO₄, ml/ml b. H₂SO₄/C₄, 1.37 1.37 1.37 1.37 1.37 1.37 1.37 1.371.37 mol/mol c. solvent/C₄ml/ml 4.9 4.9 4.9 4.9 4.9 4.9 4.9 4.9 4.9 Timeof addition C₄ 7 5.5 6.3 6.3 6.0 6.0 5.25 3.75 3.75 Hydrolysis of 100 mlH₂O 50 ml H₂O 50 ml H₂O 50 ml H₂O 100 ml H₂O 100 ml H₂O 100 ml H₂O 65 mlH₂O 65 ml H₂O the sulfate 68° C., over- 0.07 mol 0.07 mol 0.1 mol 100°C., 91° C., over- 75° C., over- 74° C., over- 80° C., over- night refluxNaOH NaOH NaCL over- night reflux night reflux night reflux night reflux85° C., over- 0.1 mol 85° C., over- night reflux night reflux NaCL nightreflux 85° C., over- night reflux Yield of 3,3-DMB 35% 49% 42% 45% 55%55% 20% 19% 36% alcohol

EXAMPLE 29

[0194] Alkylation/esterification reaction studies were conducted inwhich heptane was used as a solvent and the ratio of heptane to sulfuricacid was gradually reduced from run to run. In the final run (164), nosolvent was used. The reactions were conducted substantially as setforth in Example 28 at an ethylene pressure of 110 psig, a temperature−15 degrees C., an isobutylene addition time of 6 hours, and a molarratio of isobutylene to sulfuric acid of 2. In all but the solvent-freerun, a portion of the solvent (20 mL) was mixed with the isobutylenecharge (20 mL) in the isobutylene delivery flask. The remainder of thesolvent was charged directly to the reaction flask. Isobutylene additiontime varied from 3 to 6 hours. After an additional twenty minutes ofstirring, the ethylene pressure was released and water (100 mL) wasadded to the reaction in small portions, while the temperature wasmaintained at 0° C. The heptane layer was then separated and the acidicsulfate layer was transferred into a 500 mL two neck round bottom flask,equipped with suba seal septa in the side arm and a Vigreux column, DeanStark receiver and reflux condenser at the center neck. The resultanthydrolysis feed mixture was distilled and the water condensate collectedin the Dean Stark receiver and continuously returned to the distillationflask. The organic phase of the condensate was dried over CaCl₂ andanalyzed by GC-MC. The chromatogram showed traces of heptane,t-butyl-3,3-dimethylbutyl ether, C₆ alcohol and higher esters (notidentified). Yields of 3,3-dimethylbutanol were in the 59-63% range, butin the absence of solvent the yield was significantly reduced due tooligomerization. Process conditions and results of the runs of theseExamples are set forth in Table 16. TABLE 16 Run # 160 161 162 163 164165 166 Ethylene Pressure 110 110 110 110 110 110 110 Temperature −15−15 −15 −15 −15 −15 −15 Reactants a. H₂SO₄, mol 0.428 0.428 0.428 0.4280.428 0.428 0.428 b. C₄, mol 0.214 0.214 0.214 0.214 0.214 0.214 0.214c. solvent, ml Heptane, 200 Heptane, 100 Heptane, 50 Heptane, 25Heptane, 0 Heptane, 100 Heptane, 100 Ratios: a. solvent/H₂SO₄, 8.77 4.382.19 1.095 0 4.38 4.38 ml/ml b. H₂SO₄/C₄, 2 2 2 2 2 2 2 mol/mol c.solvent/C₄, ml/ml 10 5 2.5 1.25 0 5 5 Time of add C₄ 6 5.8 6 6 5.8 3hrs. + 2 hrs. 3 hrs + 0 (extra time) Hydrolysis of 100 ml H₂O at 100 mlH₂O at 100 ml H₂O at 100 ml H₂O at 100 ml H₂O at 100 ml H₂O at 100 mlH₂O at the sulfate 0° C., reactive 0° C., reactive 0° C., reactive 0°C., reactive 0° C., reactive 0° C., reactive 0° C., reactivedistillation distillation distillation distillation distillationdistillation distillation Weight distilled 15.4 15.3 15.6 17.3 10.3 15.215.0 product, g GC purity of the 84.0% 86.6% 86.2% 79.1% 37.9 86.6%89.7% 3-3DMB alcohol Isolated Yield of 59.0 60.1 62.6 62.6 17.8 60.161.5 3,3-DMP alcohol %

[0195] The results of Table 16 showed that isobutylene addition time didnot have a significant effect on yield.

EXAMPLE 30

[0196] Alkylation/esterification and hydrolysis reactions were carriedout substantially in the manner described in Example 28. Allalklylation/esterification reactions were conducted in a 300 mL roundbottom flask equipped with a Teflon coated power magnetic stirrer, andthe temperature was monitored by a thermocouple, inserted in a Teflonthermowell, connected to a temperature controller. The reaction flaskwas immersed in a acetone-dry ice cooling bath.

[0197] In a representative run, the 300 mL ACE round bottom reactionflask was initially charged with 98% sulfuric acid (22.8 mL; 41.9 g;0.428 mol) and heptane (30 mL). The flask was cooled to −15° C at whichpoint the ethylene pressure was slowly raised to 110 psi and maintainedat that setting during the entire run. A second 75 mL ACE flask wascharged with heptane (20 mL) and isobutylene (20 mL; 12 g; 0.214 mol).The second flask was pressurized to 120 psi and the heptane/isobutylenemixture was added dropwise to the 300 mL reaction flask at a rate of 0.2mL/min. During the addition, the temperature was kept at −15° C. Itrequired three hours for the isobutylene solution to be added over thestirred sulfuric acid-heptane suspension. The stirring was continued foran additional twenty minutes. The ethylene pressure was graduallyreleased, the temperature was raised to 0° C., and water (100 mL) wasadded at such rate the temperature did not exceed 0° C. The heptanelayer was separated and the acidic sulfate layer was transferred into a500 mL two neck round bottom flask, equipped with suba seal septa in theside arm and a Vigreux column, Dean Stark receiver and reflux condenserat the center neck. During distillation, the water condensate wascollected in the Dean Stark receiver and continuously returned to thedistillation flask. The organic condensate was collected and analyzed byGC-MC. Conditions of the reactions and results obtained are set forth inTable 17. TABLE 17 Run # 170 171 172 173 174 175 176 177 178 EthylenePressure 110 110 110 110 110 110 110 110 −110 Temperature −15 −15 −15−15 −15 −5 −5 −15 −25 Reactants a. H₂SO₄, mol 0.428 0.428 0.428 0.3210.428 0.535 0.428 0.428 0.428 b. C₄, mol 0.214 0.214 0.214 0.214 0.2140.214 0.214 0.214 0.214 c. solvent, ml Heptane, 50 Hexane, 50 Pentane,50 Heptane, 50 Heptane, 50 Heptane, 50 Heptane, 50 Heptane, 50 Heptane,50 Ratios: a. solvent/H₂SO₄, 2.19 2.19 2.19 2.92 2.19 1.75 2.19 2.192.19 mol/mol b. H₂SO₄/C₄, 2 2 2 1.5 2 2.5 2 2 2 mol/mol c. solvent/C₄ml/ml 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Time of addition 3 3 3 3 3 3 33 3 C₄ hrs. Hydrolysis of 100 ml H₂O 100 ml H₂O 100 ml H₂O 100 ml H₂O100 ml H₂O 100 ml H₂O 100 ml H₂O 100 ml H₂O 100 ml H₂O the sulfate at atat at at at at at at 0°, reactive 0°, reactive 0°, reactive 0°, reactive0°, reactive 0°, reactive 0°, reactive 0°, reactive 0°, reactivedistillation distillation distillation distillation distillationdistillation distillation distillation distillation Weight distilled16.2 14.0 16.0 12.5 16.2 16.8 15.0 15.6 15.0 Isolated yield of % 58.853.6 63.1 41.3 58.8 64.3 49.8 58.8 54.5 3,3-DMB alcohol Color crude 3,3-white white white white white white white white DMB alcohol Remarks *** * * * * * * * *the alkylsulfate was diluted with water after thesyntheses and kept at 5° C. overnight. Distilled on the next day **thehexane contains around 30-35% methylcyclopentane Run # 179 17A 17B 17CEthylene Pressure 110 110 110 110 Temperature, ° C. −15 −15 −15 −15Reactants a. H₂SO₄, mol 0.428 0.428 0.428 0.428 b. C₄, mol 0.214 0.2140.214 0.214 c. solvent, ml Heptane, 50 Heptane, 50 Heptane, 50 Heptane,50 Ratios: a. solvent/H₂SO₄, ml/ml 2.19 2.19 2.19 2.19 b. H₂SO₄/C₄,mol/mol 2 2 2 2 c. solvent/C₄ ml/ml 2.5 2.5 2.5 2.5 Time of addition C₄hrs 3 3 3 3 Hydrolysis of the sulfate 10 ml H₂O at 40 ml H₂O at 100 mlH₂O at 150 ml H₂O at 0° C. reactive 0° C. reactive 0° C. reactive 0° C.reactive distillation distillation distillation distillation Weightdistilled product, g 6.0 19.0 18.4 13.4 Isolated yield of 3,3-DMB — 47.353.7 48.3 alcohol Color crude 3,3-DMB Dark brown Dark yellow Lightyellow White alcohol Remarks * * * ** *the alkylsulfate was kept inrefrigerator at 5° C. overnight and the water added prior distillation**the alkylsulfate was diluted with water after the synthesis and keptat 5° C. overnight. Distilled next day. Run # 17D 17E 17F 17G EthylenePressure 110 110 110 110 Temperature, ° C. −15 −15 −15 −15 Reactants a.H₂SO₄, mol 0.428 0.428 0.428 0.428 b. C₄, mol 0.214 0.214 0.214 0.214 c.solvent, ml Heptane, 50 Heptane, 50 Heptane, 50 Heptane, 50 Addedsulfate additive None Yes None Yes Ratios: a. solvent/H₂SO₄, ml/ml 2.192.19 2.19 2.19 b. H₂SO₄/C₄, mol/mol 2 2 2 2 c. solvent/C₄ ml/ml 2.5 2.52.5 2.5 Time of addition C₄ hrs 3 3 3 3 Hydrolysis of the sulfate 100 mlH₂O at 100 ml H₂O at 100 ml H₂O at 100 ml H₂O at 0° C. reactive 0° C.reactive 0° C. reactive 0° C. reactive distillation distillationdistillation distillation Weight distilled product, g 18.4 21.05 16.121.3 Isolated yield 3,3-DMB 53.7 48.9 58.5 51.6 alcohol Color crude3,3-DMB Dark yellow Yellow Pale yellow White alcohol Remarks * ** ** ***the alkylsulfate was kept in refrigerator at 5° C. overnight and thewater added prior distillation *the alkylsulfate was diluted with waterafter the synthesis and kept at 5° C. overnight. Distilled next day. Run# 17H 17I 17J 17K 17L Ethylene Pressure 110 110 110 110 110 Temperature,° C. −15 −15 −15 −15 −15 Reactants a. H₂SO₄, ml/g/mol 22.8/41.9/0.42822.8/41.9/0.428 22.8/41.9/0.428 22.8/41.9/0.428 22.8/41.9/0.428 b. C₄,ml/g/mol 20/12/0.214 20/12/0.214 20/12/0.214 20/12/0.214 20/12/0.214 c.solvent, ml Heptane, 50 Heptane, 50 Decane, 50 Heptane, 50 Heptane, 50Ratios: a. solvent/H₂SO₄, ml/ml 2.19 2.19 2.19 2.19 2.19 b. H₂SO₄/C₄,mol/mol 2 2 2 2 2 c. solvent/C₄ ml/ml 2.5 2.5 2.5 2.5 2.5 Time ofaddition C₄ hrs 3 3 3 3 3 Hydrolysis of the sulfate 100 ml H₂O at 6.9 gNaOH in 100 ml H₂O at 100 ml H₂O at 100 ml H₂O at 0° C. reactive 100 mlH₂O at 0° C. reactive 0° C. reactive 0° C. reactive distillation 0° C.distillation distillation distillation distillation Weight distilledproduct, g 16 16 37.6 16.0 12.1 (w/decane) Isolated yield 3,3-DMB 48.956.0 74.4 55.2 52.4 alcohol (alcohol only) Color crude 3,3-DMB Paleyellow Yellow White Pale alcohol Remarks Distillation NaOH added toDecane kept Liquid-liquid Vacuum during under Argon** the water** duringextraction** distillation** distillation** *the alkylsulfate was kept inrefrigerator at 5° C. overnight and the water added prior distillation*the alkylsulfate was diluted with water after the synthesis and kept at5° C. overnight. Distilled next day.

[0198] In the runs of this example it was observed that: the optimumvolumetric ratio of solvent (heptane) to isobutylene was between about1.25 and about 2.5, with about 0.75 to about 1.5 mL heptane/mLisobutylene in the initial charge to the reaction flask and 0.5 to 1.0mL heptane per mL isobutylene being added with the isobutylene; pentanewas the solvent generally providing the most favorable results in thealkylation/esterification reaction; sulfuric acid to isobutylene ratiowas optimal in the neighborhood of 2.5; the optimalalkylation/esterification reaction temperature was in the range of about−15° C.; at the scale at which the reactions were conducted, the optimalisobutylene addition rate was 0.2 mL/min, and the optimal water chargeto the hydrolysis reaction was about 100 mL; the optimal temperature forwater addition was 0° C.; and addition of water immediately afteralkylation/esterification helped to minimize color bodies in the organicphase of the distillate obtained from the reactive distillation.

[0199] In the reactive distillation, it was observed that a largeportion of the alcohol accumulated in the distillation pot as a separatephase above and in contact with the acid phase, causing a decrease inselectivity and effectively lower yield. Of the stratagems used toresolve this problem, the most effective was the use of a decane as asolvent for both reaction steps. Liquid/liquid extraction was consideredas an alternative for removing the alcohol immediately upon formation;but liquid/liquid extraction was not tested in the runs of this example.

EXAMPLE 31

[0200] To a 1 L reactor was charged 96% by weight sulfuric acid (98.94g; 1 mol) and heptane (200 mL; 133.3 g, 1.33 mmol). After the system wasflushed with nitrogen, and with an approximate stir rate of 1500 rpm thereaction mass was cooled to ca. −15° C. At this temperature an overheadpressure of 120 psig ethylene was added and maintained at 120 psigthroughout the course of reaction. Five minutes after the ethylenepressure was applied a metered addition of isobutylene was initiated atthe rate of 1 mL/min (density of isobutylene=−0.59, 0.59/g/min) whilethe reaction was maintained at −15° and a metered addition of sulfuricacid (96%) was initiated at a rate of 1.25 g/min. After three hours ofsimultaneous addition of isobutylene and sulfuric acid, the sulfuricacid addition was terminated (323.6 g total sulfuric acid to thereaction, 3.17 mol) and the isobutylene addition continued for anadditional 1.5 hr with a continuous gradient beginning at 1 mL/min downto 0.5 mL/hr (2.61 mol total isobutylene added). The head pressure ofethylene was vented upon the termination of isobutylene addition (totaluptake of ethylene was 2.82 mol under these conditions). The crudereaction mass was removed from the reactor and allowed to separate intotwo liquid layers. The top layer was removed as a light yellow liquid(295.9 g, 162.6 g weight gain) while the bottom layer was a viscousyellow oil (490.3 g, 166.7 g weight gain).

[0201] Analysis of the layers was carried out by ¹H NMR in CDCl₃ viaintegration of alkylsulfate groups vs. a known amount of added toluene(internal NMR standard) to obtain a mol % 3,3-dimethylbutylsulfategroups. (46.7% yield vs. H₂SO₄; 52.5% yield vs. ethylene; 56.8% yieldvs. isobutylene).

[0202] The acid layer (490.3 g) obtained from the above reaction wasadded to a 3 L flask and to this water (980.6 g) was added dropwisewhile the acid layer was cooled in an ice bath. The resulting hydrolysisreaction mixture was then heated to a pot temperature of 99-111° C.during which an azeotrope of water and 3,3-dimethylbutanol was recoveredvia distillation. Three sequential overhead fractions were collected andanalyzed, with the results summarized in Table 18 below. TABLE 18Results from Reactive Distillation Fraction #1 Fraction #2 Fraction #3Head Temperature ° C. 73-83 83-86 86 Pot Temperature ° C.  99-108107-111 111 Weight (g, organic) 20.51 79.65 35.9 Weight 3,3-DMB alcohol(g) 8 55.4 26.6

[0203] The total weight of recovered 3,3-dimethylbutanol was 90 g (1.12mol) for an overall yield based on H₂SO₄ of 27.8%, based on ethlene of31.3% and based on isobutylene of 33.8%.

EXAMPLE 32

[0204] To a 1 L reactor was charged 96% by weight sulfuric acid (98.04g; 1 mol) and heptane (200 mL; 133.3 g; 1.33 mmol). After the system wasflushed with nitrogen, and with an appropriate stir rate of 1500 rpm thereaction mass was cooled to ca. −15° C. At this temperature an overheadpressure of 120 psig ethylene was added and maintained at 120 psigthroughout the first 3 hours of reaction. Five minutes after theethylene pressure was applied a metered addition of isobutylene wasinitiated at the rate of 1 Ml/min (Density of isobutylene=0.59, 0.59g/min) while the reaction was maintained at −15° C. and a meteredaddition of sulfuric acid (96%) was initiated at a rate of 1.56 g/min.After three hours of simultaneous addition of isobutylene and sulfuricacid, the sulfuric acid addition was terminated (380.24 g total sulfuricacid to the reaction 3.72 mol), the ethylene reservoir was closed to thereactor and the isobutylene addition continued for an additional 1.5 hrwith a continuous gradient beginning at 1 mL/min down to 0.5 mL/hr (2.61mol total isobutylene added). The head pressure of ethylene was ventedupon the termination of isobutylene addition (total uptake of ethylenewas 2.3 mol under these conditions). The reaction mass was removed fromthe reactor and allowed to separate into two liquid layers. The toplayer was removed as a light yellow liquid (166 g, 32.7 g weight gain)while the bottom layer was a viscous yellow oil (524.25 g, 144 g weightgain).

[0205] Analysis of the layers was carried out by ¹H NMR in CDCl₃ viaintegration of alkylsulfate groups vs. a known amount of added toluene(internal NMR standard) to obtain a mol % 3,3-dimethylbutylsulfategroups. (48.3% yield vs. H₂SO₄; 78.3% yield vs. ethylene; 69% yield vs.isobutylene).

[0206] The 524.25 g acid layer obtained from the above reaction wasadded to a 3 L flask and to this was added 1048.5 g water dropwise whilethe acid layer was cooled in an ice bath. The resulting hydrolysisreaction mixture was then heated to a pot temperature of 99-111° C.during which an azeotrope of water and 3,3-dimethylbutanol was recoveredvia distillation.

[0207] The total weight of recovered 3,3-dimethylbutanol was 114.6 g(1.12 mol) for an overall yield based on H2SO4 of 30.2%, based onethylene of 48.8% and based on isobutylene of 43.1%.

EXAMPLE 33

[0208] To a 1 L reactor was charged 96% by weight sulfuric acid (135 g;1.32 mol) and heptane (480 mL; 319 g). After the system was flushed withnitrogen, and with an approximate stir rate of 1500 rpm, the reactionmass was cooled to ca. −15° C. At this temperature an overhead pressureof 115 psig ethylene was added and maintained at 115 psig throughout thecourse of reaction. Five minutes after the ethylene pressure was applieda metered addition of isobutylene was initiated at the rate of 0.24mL/min (density of isobutylene=0.59, 0.14 g/min) while the reaction wasmaintained at −15° C. After three and one half hours of addition ofisobutylene (0.55 mol), the head pressure of ethylene was vented (totaluptake of ethylene was 2.28 mol under these conditions). The contents ofthe reactor were removed from the reactor and allowed to separate intotwo liquid layers. The top layer was remo0ved as a light yellow liquid(338.8 g, 14.8 g weight gain) while the bottom layer was a viscousyellow oil (168.5 g, 33.5 g weight gain).

[0209] Analysis of the layers were carried out by ¹H NMR in CDCl₃ viaintegration of alkylsulfate groups vs. a known amount of added toluene(internal NMR standard) to obtain a mol % 3,3-dimethylbutylsulfategroups. (24% yield vs. H2SO4; 13.9% yield vs. ethylene; 57.6% yield vs.isobutylene).

[0210] The acid layer (168.5 g) obtained from the above reaction wasadded to a 1 L flask and to this water (337 g) was added dropwise whilethe acid layer was cooled in an ice bath. The resulting hydrolysischarge mixture was then heated to a pot temperature of 99-111° C. duringwhich an azeotrope of water and 3,3-dimethylbutanol was recovered viadistillation.

[0211] The total weight of recovered 3,3-dimethylbutanol was 29.7 g(0.29 mol) for an overall yield based on H₂SO₄ of 22%, based on ethyleneof 12.8% and based on isobutylene of 52.8%.

EXAMPLE 34

[0212] Three batches of crude alkylsulfate were produced via theprocedures generally described in Example 33, under the particularconditions given below in Table 19, to provide the yields listed inTable 19. TABLE 19 Batch Reactions Generating Aklylsulfate Mixtures forHydrolysis Studies Batch #1 Batch #2 Batch #3 H₂SO₄ (g) initial charge98.04 98.04 98.04 H₂SO₄ addition rate (g/min) 1.45 1.68 1.6 Total H₂SO₄Addition Time 3 3 3 H₂SO₄ total (g) 359.3 399.8 386.8 H₂SO₄ (mol) 3.523.92 3.79 Isobutylene (g) 145.7 146.1 146.1 Initial Rate IsobutylenemL/min 1 1 1 Isobutylene (mol) 2.6 2.61 2.61 Ethylene Pressure (psig)120 120 120 Ethylene (g) 40.6 50.4 50.7 Ethylene (mol) 1.45 1.8 1.81Heptane (g) 133.3 133.3 133.3 Total Isobutylene addition time (hr) 4.54.5 4.5 Heptane/H₂SO₄ (wt:wt) 0.37 0.33 0.34 Isobutylene/SulfuricAddition Rate 0.71 0.61 0.65 (mol) Final Heptane wt (g) 182.6 187.7183.04 Final Acid weight (g) 484 540.2 521.4 Wt gain in Heptane (g) 49.354.5 49.7 Wt gain in acid (g) 124.7 140.4 134.6 mol 3,3-DMB esters 1.061.34 1.48 % H₂SO₄ to 3,3-DMB esters 30.1 34.2 39.1 % ethylene to 3,3-DMBesters 73.1 74.4 81.8 % isobutylene to 3,3-DMB esters 40.7 51.4 56.7

[0213] Each batch was divided into three equal parts, a control run wascarried out with one part while variations in the hydrolysis conditionswere made with the other two portions. Table 20 below summarizes theresults of this study. As indicated, one run was made with twice thehydrolysis water addition of Example 33, another with 0.5 times thewater addition, another under reflux conditions during the hydrolysis,another with addition of water to the pregnant liquor layer at reactivedistillation temperature (99°-110° C.), and still another with additionof pregnant liquor to water at that temperature. TABLE 20 HydrolysisStudies to 3,3-Dimethylbutanol Organic 3,3- % Organic Acid Water layerDMB as 3,3- % Relative Reaction wt (g) (g) (g) (g) DMB to ControlControl #1 151.3 151.3 31.42 25.67 81.7 100 2X water 151.3 352.6 28.3121.23 75.0 82.7 Reflux 151.3 151.3 26.86 20.95 78.0 81.6 Control #2175.5 175.5 40.12 28.65 71.4 100 0.5 water 175.5 87.75 42.2 32 75.8111.7 water to 175.5 175.5 ND ND ND 0 acid Control #3 170 170 36.6636.66 79.8 100 acid to 170 170 32.75 32.75 78.1 89.3 water

EXAMPLE 35

[0214] The conversion of ethylene, isobutylene and sulfuric acid to3,3-dimethylbutylsulfate, as mentioned above, is complicated by twomajor competing reactions. The competitive reaction of sulfuric acidwith ethylene resulting in the formation of ethylsulfate groups is onecompetitive pathway which would be expected to become more significantwith an increase in ethylene pressure (concentration increase).Significantly, the other major side reaction, the oligomerization ofisobutylene would be expected to increase with an increase in therelative amounts of isobutylene vs. ethylene. These competitive sidereactions, because of their diametrically opposed relationship to therelative concentration of each olefin, necessitates an optimal range ofconditions/concentrations for the desired formation of3,3-dimethylbutylsulfate. Example 7, supra, describes conditions whichgenerated 3,3-dimethylbuytlsulfate with high selectivity by thecontinuous introduction of sulfuric acid and isobutylene to a reactionzone containing heptane and ethylene. The first column of Table 21 belowsummarizes the results from this procedure. In continuing studies ofthis reaction, the scale was increased from a 100 cc reaction zone to a1 liter reaction zone. Table 21 below further summarizes the resultsobtained by transferring the conditions described for the small scalereaction to the one liter scale. TABLE 21 One Liter Reactor Studies for3,3-Dimethylbutylsulfate 100 cc 1 L 1 L-ethylene hold patent H₂SO₄ (g)charge 5 98.04 98.04 135 H₂SO₄ addition rate 0.08 1.25 1.56 0 (g/min)Total H₂SO₄ Addition 3 3 3 0 Time H₂SO₄ total (g) 19.8 323.6 380.24 135H₂SO₄ (mol) 0.194 3.17 3.72 1.32 Isobutylene (g) 9.7 146 146 30.9Initial Rate Isobutylene 0.056 1 1 0.24 mL/min Isobutylene (mol) 0.1732.61 2.61 0.55 Ethylene Pressure (psig) 120 120 120 115 Ethylene (g)6.78 78.96 64.4 63.84 Ethylene (mol) 0.242 2.82 2.3 2.28 Heptane (g)6.65 133.3 133.3 319 Total Isobutylene 6 4.5 4.5 3.5 Addition time (hr)Heptane/H₂SO₄ (wt:wt) 0.35 0.41 0.35 2.36 Isobutylene/Sulfuric 0.72 0.830.66 N/A Addition Rate (mol) Final Heptane wt (g) 7.74 295.9 166 333.79Final Acid weight (g) 30.7 490.3 524.25 168.5 Wt gain in Heptane (g) 0.9162.6 32.7 14.79 Wt gain in acid (g) 11.1 166.7 144.01 33.5 mol 3,3-DMBesters 0.114 1.48 1.8 0.318 mol ethyl esters 0.011 ND 0.2 0.056 % H₂SO₄to 3,3-DMB 59 46.7 48.3 24.0 esters % ethylene to 3,3-DMB 47 52.5 78.313.9 esters % isobutylene to 3,3- 66 56.8 69.0 57.6 DMB esters wateradded for — 980.6 1048.5 337 distillation (g) 3,3 DMB recovered — 90114.6 29.7 mol 3,3-DMB recovered — 0.88 1.12 0.29 % H₂SO₄ to 3,3-DMB —27.8 30.2 22.0 % ethylene to 3,3-DMB — 31.3 48.8 12.8 % isobutylene to —33.8 43.1 52.8 3,3-DMB

EXAMPLE 36

[0215] Typically, at the completion of isobutylene addition, thereaction is terminated by the release of any excess ethylene pressure inthe reactor system (Reaction under a constant pressure of ethylene). Toreduce the loss in yield associated with this ethylene purge from thesytem reaction conditions were explored which reduced the ethylenecontent in the reaction system prior to venting the system. A summary ofthe results obtained by closing the reactor system to a continuous feedof ethylene after 3 hours of total reaction time (the point at which theaddition of sulfuric acid was complete) is given in Table 21 above.

[0216] It will be seen that the yield of product based on consumedethylene dramatically increased as a result of less ethylene lost due tothe purge at the completion of reaction.

[0217] As a result of the changes in process parameters described above,significant advantages in yield and in productivity (lbs. product vs.volume of reactants/solvent) were achieved.

EXAMPLE 37

[0218] Catalytic dehydrogenation runs were conducted comparing theeffect of varying the loading of a catalyst material commerciallyavailable from Engelhard Corporation.

[0219] XRF analysis of the commercial catalyst as received fromEnglehard Corporation, Cu-0330 XLT, gave the following elementalcomposition: Element % Na 1.2 Al 14.9 Si <0.1 Ca <0.1 Mn <0.1 Cu 37.4

[0220] Physical Property measurements as supplied by Engelhard are givenin Table 22 below. TABLE 22 Catalyst Properties Catalyst Cu-0330XLTSurface Area (m/g) 30 Pore volume (ml/g) 0.16 Density (g/mL) 1.63 Crushstrength (lb/mm) 11.3 particle type tablet particle size (diameter 0.125in inches)

[0221] B.E.T. surface area and pore volume analyses were performed,yielding the following data: BET Surface Area 26.6 m²/g Total PoreVolume 0.118 cm³/g

[0222] Runs were conducted to compare the effect of three differentcatalyst loadings (1 g, 2 g and 4 g) at a total flow of 200 sccm (3.33cm s⁻¹) feed gas, comprised of 5% alcohol of 94% purity (remainder aswater), helium as diluent, at ca. 320° C. bed temperature. In thereaction run conducted at a 1 g catalyst loading, conversion to aldehydeincreased from about 58% to about 90% in the first hour after startup,then immediately commenced to decay, declining linearly until the runwas terminated about 24 hours after startup. Conversion at 24 hours wasabout 75%.

[0223] In the reaction run at 4 g catalyst loading, conversion toaldehyde began at about 93%, dipped to about 90% in the first severalhours, recovered to about 93% after 4 hours, and was maintained at92-94% until about 90 hours, after which it gradually tapered off, toabout 92% at 100 hours, 90% at 125 hours, and 88% at the end of the run(142.5 hours).

[0224] In the run using an intermediate catalyst loading (2 g), theconversion to aldehyde increased from about 63% to 90% in the first houror two, held close to 90% until about 21 hours, then progressivelydeclined to about 86% after about 37 hours, whereupon the run wasterminated.

[0225] The implication of the above results is that onset ofdeactivation is not linearly related to increase in catalyst weight. Ata constant flow the change in catalyst weight directly influences thecontact time of gases on catalyst surface.

[0226] Contact Time=(Catalyst Volume)/(Total Flow of Gases) Grams ofTime to Catalyst Catalyst Volume Contact Time Deactivation (hr) 1 0.613cm³ 0.184 s  0 2 1.223 cm³  0.37 s 21 4  2.45 cm³  0.74 s 90

[0227] Extrapolation of these data suggests that an 8 g catalyst bedoperated under the feed composition, temperature, and flow conditions ofthis example would not begin to deactivate until after about 340 hr ofoperation.

[0228] It is natural to suspect that an increase in catalyst might causea decrease in selectivity (higher number of active sites mightcorrespond to a greater probability of secondary reactions). However,analysis of product gases established that, in the 4 g catalyst run,selectivity was maintained in excess 98% after the first three or fourhours, and very gradually increased throughout the remainder of the runto a value slightly over 99% at the end (142.5 hours). At a catalystloading of 1 g, selectivity progressively increased from about 97% atthe beginning of the run to about 98.5% or 98.7% at the end (24 hours).At a a loading of 2 g, selectivity was worse than for either of theother runs, generally increasing from about 95.2 to 95.4% early in therun to about 97.6 to 97.8% at the end, with several excursions below95%. Thus, in the range of catalyst loadings which provide optimalcatalyst life, selectivity does not decrease with added catalyst; infact, the selectivity is slightly higher in the case with the largestamount of catalyst tested (also, selectivity appears to slightly gain infavor of aldehyde formation with time on stream).

[0229] The added catalyst weight (volume) at a constant flow has adirect impact on productivity of catalyst.

[0230] Productivity=quantity of product produced per unit catalyst perunit time; P=mmol aldehyde/gram catalyst hour

[0231] Operation at 200 sccm feed gas containing 5% by volume3,3-dimethylbutanol and a catalyst loading of 4 g translates into aproductivity of 6 mmol product per gram catalyst per hour (0.6 kg/kghr). Once deactivation takes place (as evidenced by a decrease inaldehyde production and an increase in alcohol exiting the reactor),rate constants for the linear portion of the deactivation can becalculated (see Table 23, below).

[0232] The deactivation rate not only decrease in magnitude with anincrease in catalyst, the reduction in rate is not a linear responsewith additional stability gained by addition of more catalyst. TABLE 23Deactivation vs. Catalyst Loading grams mmol alcohol/ Productivity/ catslope g cat hr deactivation 1 0.7399 25.1 34.0 2 0.2381 12.6 52.8 40.1156  6.3 54.4

[0233] The effects of this non-linearity can be related to productivityand is shown in the last column in the table above (a linear responsewould give a constant Productivity/Deactivation).

[0234] The above analysis suggests that an increase in catalyst chargewill extend the overall lifetime of catalyst by 1) increasing the timeon stream prior to observable deactivation and 2) decreasing the rate ofdeactivation. Because the benefit gained from increased catalyst lifesurpasses the penalty associated with decrease in catalyst productivity,it may be desirable in commercial operation to use a catalyst loadingsignificantly in excess of that necessary for satisfactory conversion atstartup. For example, at an alcohol content in range of about 4-6% byvolume in the feed gas to the reactor, it may be especially preferred toprovide a catalyst charge sufficient so that the normal operating spacevelocity is less than about 2.0 sec⁻¹, more preferably between about 1.0and about 1.5 sec⁻¹. A space velocity in the latter range extends thecatalyst life while maintaining a reasonable productivity, e.g., in therange of between about 0.45 and about 0.75 kg 3,3-dimethylbutanal/gramcatalyst-hour.

EXAMPLE 38

[0235] In a further series of anaerobic dehydrogenation runs, the feedgas flow rate was varied (150-300 sccm) at a constant flow of alcoholfeed (variable %) and constant weight of catalyst (2 g of Cu-0330XLT). Aplot showing the results for aldehyde formation is shown below. Thevariation in flow rate at a constant charge results in a variation incontact time. A constant flow of alcohol (10 sccm) results in a variable% alcohol in stream. Flow Rate Contact Time % Alcohol 300 sccm 0.123 s3.33 200 sccm 0.184 s 5   150 sccm 0.245   6.67

[0236] With a constant flow of alcohol, although the total flow varies,productivity should not be affected as long as conversion is constant.Comparative data for these runs indicated little change in aldehydeproduction (nor, therefore, conversion of alcohol) resulted fromvariations in total gas flow rate at constant alcohol rate. However,selectivity was found to decline with increasing gas concentration tothe extent that, after 20 hours on stream time, selectivity at 200 sccmand 5% gas strength had risen moderately to about 98%, while selectivityat 150 sccm and 6.67% gas strength had progressively declined to about94.5%. Interestingly, selectivity at 300 sccm and 3.33% gas fell inbetween, i.e., just short of 97% at 19 hours. Selectivities may showfurther divergence at the longer reaction times.

[0237] Considering the dependence of catalyst life on catalyst loadingrelative to 3,3-dimethylbutanol feed rate, together with theindependence of performance effects from total flow rate, a preferredmode of operation may be expressed in terms of the product of spacevelocity and the volume fraction of 3,3-dimethylbutanol in the feed gas,which should be in the range of 0.05 to about 0.08 (cc alcohol)(cc feedgas-sec)⁻¹.

EXAMPLE 39

[0238] Under commercial operating conditions a common diluent such asnitrogen would be preferred to helium (all of the above examples usedhelium to dilute the alcohol). Replacement of helium with nitrogen asthe diluent was investigated using 1 g Cu-0330XLT with 5% alcohol at atotal flow of 200 sccm and a ca. 310° C. bed temperature. No majoreffect on the conversion to aldehyde resulted from using N₂ in place ofHe as the diluent.

EXAMPLE 40

[0239] In the runs of this example, copper catalyst which had beendeactivated in the course of dehydrogenation runs was subjected tooxidative regeneration conditions.

[0240] From TEM studies it appears that deactivation may be related tothe sintering of copper particles. The sintering effect (agglomerationof particles) causes a reduction in copper surface area and therefore,which may result in a reduction in active sites. This agglomerationphenomena is not well understood. Tests were run to determine whetherre-oxidation of the copper particles would re-disperse the copper and,therefore, increase its surface area.

[0241] Initial efforts focused on the introduction of oxygen (diluted to10% in helium) at a reaction temperature equivalent to normal operationconditions (ca. 320° C.). A series of three dehydrogenation cycles wererun, with two intermediate regeneration cycles.

[0242] Dehydrogenation reactions were conducted by introducing a feedgas containing 5% by volume 3,3-dimethylbutanol in helium at a rate of200 sccm into a catalyst bed containing 1 g Cu0330XLT catalyst, operatedat a temperature of 320° C.

[0243] The first oxidative “regeneration” of catalyst was actually foundto have a negative impact on conversion of alcohol to aldehyde as wellas a negative effect on stability (slope of conversion vs. timerelationship). Conversion at the end of the first cycle was about 80%after 10 hours. Immediately after regeneration, conversion was quitelow, recovering to a maximum of only about 70% before tapering offagain. However, the second regeneration cycle proved effective torestore the conversion vs. time profile for the catalyst toapproximately the same level of performance as displayed during thesecond cycle.

[0244] Examination of the temperature change associated with theintroduction of oxygen into the “reduced” (used) catalyst bed revealedthat an exothermic event took place (presumably the oxidation of reducedcopper to copper oxides). Because of the possibility that thesignificant exotherm may have actually caused further sintering of thecatalyst, further investigations were conducted under milder“regeneration” conditions. In the latter tests, a regeneration gascontaining 10% oxygen (diluted with helium) was introduced at a bedtemperature of 250

C between dehydrogenation cycles. An exothermic event again took placeupon addition of oxygen which appeared to be complete within 30 minutesof treatment. However, unlike the regeneration with oxygen at 320□C,milder treatment at 250° C. restored a greater % of activity to thecatalyst. The selectivity of the catalyst was only slightly affected bythe treatment. Operating data from dehydrogenation runs followingregeneration at 250° C. demonstrated that the first regeneration causeda rejuvenation of activity (ca. 55% based on the extent of deactivationas evidenced by % aldehyde produced). The second regenerative treatmentcaused a greater % of reactivation (although the net activity graduallydecreased from cycle to cycle).

EXAMPLE 41

[0245] A series of dehydrogenation runs was conducted comparing theeffect of catalyst loading (1 g, 2 g, and 4 g) at a total flow of 200sccm (3.33 cm s⁻¹) feed gas, comprised of 5% alcohol of >99% purity,helium as diluent. At ca. 320□C bed temperature, it was found thatselectivity in the dehydrogenation run with 4 g catalyst selectivity wassharply lower during the first 15 to 20 hours than in the runs using 1 gor 2 g catalyst. The 1 g and 2 g catalyst beds afforded selectivities ofwell over 90% substantially throughout the dehydrogenation run. Duringthe run using the 4 g bed, selectivity dropped precipitously from anearly level above 90% to a level below 70% at about 6 or 7 hours, thenrose steadily to a level above 90% at 20 hours, maintaining that levelin subsequent operation. Productivity in the production of aldehydeessentially followed the same pattern as selectivity.

[0246] Analysis of the by-products produced in the 4 g of catalystreaction revealed that the increase in catalyst (increase in contacttime) gave rise to a large early increase in both the olefin and esterforming reactions. The extent of formation of both of these by-productsdecreased in importance with time (thereby giving rise to an increase inaldehyde selectivity).

[0247] Attempts to increase the performance of Cu-0330CE under excesscatalyst conditions (longer contact times) were made by 1) decreasingthe bed temperature and by 2) variation of the “ramping” conditions usedto bring the catalyst bed to reaction temperature (standard temperatureprofiles for all reactions, unless noted otherwise include an initialramp period of 2 hr starting at 250□C). Different temperature profileswere used for three dehydrogentation reaction runs with 4 g ofCu-0330CE. In the first run, reflecting the conditions typically used inthe examples above, the bed temperature was ramped from 250° C. to ca.310□C in about 2 hours and maintained at ca. 310° C.; in the second run,the temperature was ramped from about 210° to about 280° C. in about 2hours and held at 280° C.; in the third run the temperature was held atabout 210° C. for about 4 hours, ramped to about 280° C. over a periodof about 2 hours, then held at about 280° C.

[0248] Lowering the maximum reaction temperature from 310□C to 280□C(bed temperature) brought about a significant increase in selectivity toaldehyde and overall aldehyde productivity during the first ten hours ofoperation. Imposing a 4 hr. hold at 220□C provided minimal additionaladvantage in early selectivity, and resulted in a significant penalty inconversion.

[0249] Although lowering the reaction temperature to 280° C. was foundeffective to establish high selectivity at reasonable productivity earlyin the dehydrogenation run, lowering the reaction temperature adverselyaffects the reaction equilibrium, thereby unavoidably lowering theachievable conversion. In an industrial manufacturing facility operatedat temperatures below 300° C., it may be necessary to remove unreacted3,3-dimethylbutanol from the 3,3-dimethylbutanal product of thedehydrogenation, e.g., by distillation, and recycle the alcohol to thedehydrogenation reaction. In each case, the benefit in extended catalystlife achieved by operation at 280° or 290° C. would need to be weighedagainst the increase in capital and operating associated with incompleteconversion and recycle of 3,3-dimethylbutanol to the dehydrogenationreactor. Moreover, at operating temperatures significantly lower than275° C., catalyst life may actually suffer.

EXAMPLE 42

[0250] Inasmuch as the solubility of water in 3,3-dimethylbutanol isabout 6% by weight, the feed gas to an industrial reactor forpreparation of 3,3-dimethylbutanal would typically contain about 6%water (13.6 mol %) on an alcohol basis. Dehydrogenation runs wereconducted in the manner described in Example 41 (except that 4 gcatalyst were used at 280□C bed temperature; Cu-0330CE catalyst) using a94% 3,3-dimethylbutanol/6% water mixture. The only observabledifferences noted by this substitution is a shift in by-productproduction from olefin and ester to carboxylic acid.

EXAMPLE 43

[0251] Regeneration of Cu-0330CE was investigated by oxygen (10% inhelium) at 250□C on a used 1 g sample. Three dehyrogenation cycles wererun, each at 320° C., a feed gas rate of 200 sccm, and a3,3-dimethylbutanol content in the feed gas of 5%. In the first run,conversion to 3,3-dimethylbutanal was essentially stable at around 88%throughout a 75 hour run. In the second run (after the firstregeneration cycle), conversion to 3,3-dimethylbutanal decayedessentially linearly from about 87% to about 85% over the first 50hours, then somewhat more sharply from 85% to about 82% over the next 15hours. In the third run (after the second regeneration cycle),conversion decayed linearly from about 86% at the outset to about 84%after 20 hours.

[0252] Although oxygen treatment appears to only cause detrimentaleffects on the performance of the catalyst, conclusions are difficult todraw based on the longevity of this particular catalyst (after 75 hrs.of continuous operation, no significant loss in activity was observed).It is entirely possible that the oxygen treatment had little bearing onthe outcome of the performance as evidenced by the pattern of by-productformation. Very little change in olefin production was seen from the endof cycle one to the beginning of cycle two. The pattern suggests thenormal drop in olefin production with time. The ester formation didchange with a greater production of this by-product with each succeedingcycle. The acid production, very negligible in all cases, did not appearto alter from its normal pattern with each successive cycle. The etherformation may slightly increased with each cycle; however, the changeswere minimal and may follow a continuous progression.

EXAMPLE 44

[0253] ZnO (CaO added as stabilizer) was evaluated as a dehydrogenationcatalyst under standard conditions of 5 wt % alcohol in a total flow of200 sccm gases at various temperatures.

[0254] Conversions were not as good as those demonstrated for Cucatalysts. Yield of aldehyde stablized at about 33-35% at a temperaturein the range of 370° C. Increasing the temperature to 400° C. resultedin an increase of aldehyde yield to about 45-46%, from which itdeteriorated over the next two hours to about 40%. Selectivity toaldehyde was in the neighborhood of 80-85%.

EXAMPLE 45

[0255] The anaerobic catalytic dehydrogenation reaction described indetail above is commercially attractive only at high temperature due tothermodynamic constraints. The introduction of oxygen to thedehydrogenation renders the overall reaction exothermic and thereforethermodynamically more favorable. This should allow for operation atsubstantially lower temperatures (in cases where the dehydrogenation isoperating under thermodynamic constraints and not kinetic constraints).

[0256] Oxidative dehydrogenation was investigated using ZnO catalystdescribed above. A feed gas containing 5% by volume 3,3-dimethylbutanolwas introduced into a tubular reactor containing ZnO catalyst (4 g).Oxygen was initially introduced into the feed gas at concentration ofabout 1.5% by volume. Oxidative dehydrogenation was initiated underessentially adiabatic conditions with the temperature rising from about260° to about 320° C. After about one hour and forty minutes ofoperation, the oxygen fraction was increased to about 2.5% by volume andreaction continued at 350° C. Aldehyde yield gradually increased from 0to about 30% over the first hour and stabilized at that level as long asthe oxygen concentration was maintained at 1.5%. When the oxygenconcentration was stepped up to 2.5%, the aldehyde yield stepped up toabout 40% and stayed at about that level through the remainder of therun, i.e., for a little less than two hours after the oxygenconcentration was increased. Selectivities ranged from about 85-90% at1.5% oxygen and in the neighborhood of 80% at 2.5% oxygen.

[0257] Although conversions and selectivities of oxidativedehydrogenation over ZnO were not as favorable as those for anaerobicdehydrogenation over a copper catalyst, the addition of oxygen at 2.5%provided slightly higher 3,3-dimethylbutanol yields at 350° C. than wasachieved by anaerobic dehydrogenation over ZnO at 365° C.

[0258] The addition of oxygen (at least up to 2.5% oxygen in thereaction stream) has a positive effect on aldehyde generation (asevidenced by the gain in production from 1.5% to 2.5% oxygen) withoutany noticeable change in selectivity. A comparison (not exactly a directcomparison with a 15□C difference in temperature) between the reactionconducted under oxygen free conditions and the above oxygen experimentis shown below.

[0259] Again, a clear gain in conversion was observed. The by-productsproduced in this study are shown below.

[0260] The most dominant by-product is olefin formation which isdependent on the concentration of added oxygen.

[0261] In view of the above, it will be seen that the several objects ofthe invention are achieved and other advantageous results attained.

[0262] As various changes could be made in the above compositions andprocesses without departing from the scope of the invention, it isintended that all matter contained in the above description and shown inthe accompanying drawings shall be interpreted as illustrative and notin a limiting sense.

What is claimed is:
 1. A process for the preparation of3,3-dimethylbutanal comprising: preparing an ester of3,3-dimethylbutanol by reacting isobutylene, ethylene and said mineralacid; hydrolyzing said ester to produce 3,3-dimethylbutanol; andconverting 3,3-dimethylbutanol to 3,3-dimethylbutanal.
 2. A process asset forth in claim 1 wherein preparation of said ester comprisescontacting ethylene and isobutylene with sulfuric acid, thereby forminga sulfuric acid ester of 3,3-dimethylbutanol.
 3. A process as set forthin claim 2 wherein reaction of isobutylene, ethylene and sulfuric acidproduces an ester reaction product selected from the group consisting of3,3-dimethylbutyl hydrogensulfate, bis(3,3-dimethylbutyl) sulfate,3,3-dimethylbutyl ethyl sulfate, and mixtures thereof.
 4. A process asset forth in claim 2 wherein isobutylene and ethylene are substantiallysimultaneously brought into contact with sulfuric acid.
 5. A process asset forth in claim 4 wherein ethylene and isobutylene are introducedinto a condensed phase reaction medium comprising an organic solvent andsulfuric acid.
 6. A process as set forth in claim 5 wherein a feedsolution containing an organic solvent and a hydrocarbon reactantselected from the group consisting of ethylene, isobutylene and mixturesthereof is introduced into a condensed phase reaction medium comprisingsulfuric acid.
 7. A process as set forth in claim 5 wherein a streamcomprising sulfuric acid and a feed solution containing an organicsolvent and a hydrocarbon reactant selected from the group consisting ofethylene, isobutylene and mixtures thereof are introduced simultaneouslyinto an alkylation/esterification reaction zone.
 8. A process as setforth in claim 5 wherein isobutylene and ethylene are continuously orintermittently introduced into said condensed phase reaction medium inan alkylation/esterification reaction zone, and analkylation/esterification reaction mixture comprising 3,3-dimethylbutylsulfate is continuously or intermittently withdrawn from said reactionzone.
 9. A process as set forth in claim 5 wherein isobutylene andsulfuric acid are simultaneously added to a batch reaction vesselpressurized with ethylene.
 10. A process as set forth in claim 9 whereinsulfuric acid is added at molar rate in excess of the molar rate ofaddition of isobutylene, the molar ratio of the rate of sulfuric acidaddition to the rate of isobutylene addition being between about 1.2 andabout 1.7, the addition of sulfuric acid being substantially completebetween about one and about five hours before the addition ofisobutylene is completed.
 11. A process as set forth in claim 10 whereinthe integrated average molar ratio of the rate of isobutylene additionto the rate of sulfuric acid addition during sulfuric acid addition isbetween about 0.6 and about 0.75.
 12. A process as set forth in claim 5wherein the volumetric ratio of solvent to sulfuric acid in saidalkylation/esterification reaction zone during saidalkylation/esterification reaction is not greater than about 4:1.
 13. Aprocess as set forth in claim 12 wherein said volumetric ratio ofsolvent to sulfuric acid is not greater than about 3:1.
 14. A process asset forth in claim 13 wherein said volumetric ratio of solvent tosulfuric acid is not greater than about 2.5:1.
 15. A process as setforth in claim 14 wherein said volumetric ratio is between about 1 andabout 2.5:1.
 16. A process as set forth in claim 2 wherein ethylene,isobutylene and sulfuric acid are brought together in analkylation/esterification reaction zone at a temperature above thecritical temperature for ethylene.
 17. A process as set forth in claim 1wherein the reaction is conducted at a temperature below about 10° C.18. A process as set forth in claim 1 wherein: analkylation/esterification reaction mixture comprising a sulfuric acidester of 3,3-dimethylbutanol is obtained by reaction of ethylene,isobutylene and sulfuric acid in the presence of an organic solvent,said reaction mixture comprising an organic phase and a pregnant liquorphase, said organic phase comprising said solvent, and said pregnantliquor phase containing said ester and said mineral acid; said pregnantliquor phase is separated from said organic phase; and 3,3-dimethylbutylsulfate contained in said pregnant liquor phase is hydrolyzed to produce3,3-dimethylbutanol.
 19. A process as set forth in claim 18 whereinhydrolysis produces a hydrolysis reaction mixture comprising a spentacid phase and an organic hydrolyzate phase comprising3,3-dimethylbutanol.
 20. A process as set forth in claim 19 wherein saidorganic hydrolyzate phase is distilled for recovery of3,3-dimethylbutanol.
 21. A process as set forth in claim 20 wherein,prior to distillation thereof, said organic hydrolyzate phase iscontacted with a base for neutralization of residual mineral acidcontained therein.
 22. A process as set forth in claim 18 wherein ahydrolysis feed mixture comprising said pregnant liquor is heated in thepresence of water in a reactive distillation hydrolysis reaction zone toeffect hydrolysis of said ester and distillation of 3,3-dimethylbutanolfrom the hydrolysis reaction mixture.
 23. A process as set forth inclaim 22 wherein said hydrolysis feed mixture is prepared by introducingwater into said pregnant liquor, the heat of dilution being removed bycooling during addition of water to maintain the temperature of thediluted pregnant liquor not greater than about 50° C. substantiallythroughout the course of dilution thereof.
 24. A process as set forth inclaim 23 wherein said hydrolysis feed mixture is continuously orintermittently introduced into said hydrolysis reaction zone, heat isintroduced into said reaction zone for distillation of3,3-dimethylbutanal therefrom, an overhead stream comprising3,3-dimethylbutanal is continuously removed from said reaction zone, anda bottoms stream comprising spent sulfuric acid is continuously orintermittently removed from said reaction zone.
 25. A process as setforth in claim 22 wherein water is added to said pregnant liquor in awater/pregnant liquor weight ratio between about 0.3 and about 0.7. 26.A process as set forth in claim 18 wherein said pregnant liquor is mixedwith a stoichiometric excess of base to raise the pH sufficiently foralkaline hydrolysis.
 27. A process as set forth in claim 1 wherein3,3-dimethylbutanol is contacted with an oxidizing agent for theoxidation of the alcohol to 3,3-dimethylbutanal.
 28. A process as setforth in claim 27 wherein said oxidizing agent comprises copper oxideeffective for stoichiometric oxidation of an alcohol to a correspondingaldehyde.
 29. A process as set forth in claim 1 wherein3,3-dimethylbutanol is contacted with a catalyst effective fordehydrogenation of 3,3-dimethylbutanol to 3,3-dimethylbutanal.
 30. Aprocess as set forth in claim 29 wherein said catalyst is effective forthe anaerobic dehydrogenation of 3,3-dimethylbutanol, said catalystbeing contacted with 3,3-dimethylbutanol in the substantial absence ofmolecular oxygen.
 31. A process as set forth in claim 29 wherein saidcatalyst is effective for the oxidative dehydrogenation of3,3-dimethylbutanol, said catalyst being contacted with3,3-dimethylbutanol and molecular oxygen.
 32. A process as set forth inclaim 29 wherein said catalyst comprises an active phase comprising areduced form of copper obtained in a stoichiometric redox reactionbetween copper oxide and 3,3-dimethylbutanol.
 33. A process as set forthin claim 29 wherein said catalyst comprises an active phase comprising areduced form of copper obtained by contacting copper oxide with areducing agent selected from the group consisting of molecular hydrogen,sodium borohydride, hydrazine.
 34. A process as set forth in claim 29wherein vapor phase 3,3-dimethylbutanol is passed over a bed comprisinga catalyst for the dehydrogenation of 3,3-dimethylbutanol to3,3-dimethylbutanal.
 35. A process as set forth in claim 34 wherein saidcatalyst is effective for the anaerobic dehydrogenation of3,3-dimethylbutanol, said vapor phase being substantially free ofmolecular oxygen.
 36. A process as set forth in claim 34 wherein saidcatalyst is effective for the oxidative dehydrogenation of3,3-dimethylbutanol, said vapor phase comprising molecular oxygen.
 37. Aprocess as set forth in claim 1 wherein isobutylene and ethylene arebrought into contact with sulfuric acid in an alkylation/esterificationreaction zone without introduction of any organic solvent into saidreaction zone from any extraneous source.
 38. A process as set forth inclaim 1 wherein said 3,3-dimethylbutanal is reacted withL-α-aspartyl-L-phenylalanine 1-methyl ester in the presence of areducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.39. A process as set forth in claim 1 wherein the t-butylacetic acidcontent of the product 3,3-dimethylbutanal is less than about 1% byweight.
 40. A process for the preparation of 3,3-dimethylbutanalcomprising contacting 3,3-dimethylbutanol with a catalyst for thedehydrogenation of an alcohol to a corresponding aldehyde at a turnoverratio of at least 5 moles 3,3-dimethylbutanal per mole catalyst activephase prior to any interruption of the reaction for regeneration of thecatalyst.
 41. A process as set forth in claim 40 wherein vapor phase3,3-dimethylbutanol is passed over a catalyst bed comprising a catalystfor the dehydrogenation of 3,3-dimethylbutanol to 3,3-dimethylbutanal.42. A process as set forth in claim 41 wherein said catalyst iseffective for the anaerobic dehydrogenation of 3,3-dimethylbutanol, saidcatalyst being contacted with 3,3-dimethylbutanol in the substantialabsence of molecular oxygen.
 43. A process as set forth in claim 41wherein said catalyst is effective for the oxidative dehydrogenation of3,3-dimethylbutanol, said catalyst being contacted with3,3-dimethylbutanol and molecular oxygen.
 44. A process as set forth inclaim 41 wherein said catalyst is selected from the group consisting ofcopper oxide, a reduced form of copper, zinc oxide, silver, gold,platinum, palladium and a platinum/tin alloy.
 45. A process as set forthin claim 44 wherein said catalyst comprises a reduced form of copper.46. A process as set forth in claim 40 wherein said catalyst does notcontaminate the 3,3-dimethylbutanol with impurities toxic to humans. 47.A process as set forth in claim 40 wherein said catalyst issubstantially non-toxic to humans.
 48. A process as set forth in claim40 wherein the dehydrogenation is conducted at a temperature of at leastabout 200° C.
 49. A process as set forth in claim 48 wherein saiddehydrogenation is conducted at a temperature between about 200° C. andabout 400° C.
 50. A process as set forth in claim 49 whereindehdyrogenation is conducted at temperature between about 275° C. andabout 345° C.
 51. A process as set forth in claim 50 whereindehydrogenation is conducted at a temperature between about 305° C. andabout 330° C.
 52. A process as set forth in claim 50 whereindehydrogenation is conducted at a temperature between about 275° C. andabout 295° C.
 53. A process as set forth in claim 50 whereindehydrogenation is started up and operated during a phase in period at atemperature between about 2400 and about 270° C., and thereafteroperated at between 275° C. and about 345° C., said phase in periodbeing long enough so that the yield of 3,3-dimethylbutanol of at least85% is achievable from about 90 minutes after the beginning thereofuntil a turnover ratio of at least 5 moles 3,3-dimethylbutanal per molecatalyst active phase has been achieved.
 54. A process as set forth inclaim 49 wherein the reaction is conducted at a total pressure of notgreater than about 100 psig and a hydrogen partial pressure of less thanabout 100 psig.
 55. A process as set forth in claim 54 wherein thehydrogen partial pressure is between about 5 psig and about 20 psig. 56.A process as set forth in claim 54 wherein said 3,3-dimethylbutanal isreacted with L-α-aspartyl-L-phenylalanine 1-methyl ester in the presenceof a reducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.57. A process as set forth in claim 40 wherein a gas phase comprising aninert gas and initially containing at least about 0.5% by volume3,3-dimethylbutanol is passed over a fixed or fluid catalyst bedcomprising a catalyst for the dehydrogenation of 3,3-dimethylbutanol.58. A process as set forth in claim 57 wherein the initial concentrationof 3,3-dimethylbutanol in said gas phase is between about 1% and about25% by volume.
 59. A process as set forth in claim 57 wherein said gasphase initially contains between about 2.5% and about 10% by volume3,3-dimethylbutanol.
 60. A process as set forth in claim 57 wherein3,3-dimethylbutanol is dehydrogenated to 3,3-dimethylbutanal over saidcatalyst bed at a temperature of at least about 250° C.
 61. A process asset forth in claim 60 wherein said gas phase flows over said catalystbed at a space velocity of at least about 0.25 sec⁻¹.
 62. A process asset forth in claim 57 wherein said catalyst is effective for theanaerobic dehydrogenation of 3,3-dimethylbutanol, said vapor phase beingsubstantially free of molecular oxygen.
 63. A process as set forth inclaim 62 wherein the space velocity is between about 1.0 and about 2.0sec⁻¹.
 64. A process as set forth in claim 63 wherein the space velocityis between about 1.0 and about 1.5 sec⁻¹.
 65. A process as set forth inclaim 62 wherein the product of the product of the space velocity andthe initial volume fraction of 3,3-dimethylbutanol in the gas phasepassed over the catalyst bed is controlled in the range of 0.05 to about0.08 (cc alcohol)(cc feed gas-sec)⁻¹.
 66. A process as set forth inclaim 57 wherein said gas phase initially contains about 6% by weightwater vapor, basis 3,3-dimethylbutanol.
 67. A process as set forth inclaim 57 wherein said catalyst is effective for the oxidativedehydrogenation of 3,3-dimethylbutanol, said vapor phase comprisingmolecular oxygen.
 68. A process as set forth in claim 57 wherein saidcatalyst comprises a reduced form of copper.
 69. A process as set forthin claim 68 wherein said catalyst comprises copper on an inert supportselected from the group consisting of silica, alumina and mixturesthereof, titania, zirconia, zeolite, baryte, kieselguhr, and controlledpore glass.
 70. A process as set forth in claim 68 wherein said catalystis prepared by in situ reduction of copper oxide in the stoichiometricoxidation of 3,3-dimethylbutanol to 3,3-dimethylbutanal.
 71. A processas set forth in claim 68 wherein said catalyst comprises an active phasecomprising a reduced form of copper obtained by contacting copper oxidewith a reducing agent selected from the group consisting of molecularhydrogen, sodium borohydride and hydrazine.
 72. A process as set forthin claim 40 wherein said 3,3-dimethylbutanal is reacted withL-α-aspartyl-L-phenylalanine 1-methyl ester in the presence of areducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.73. A process as set forth in claim 40 wherein the t-butylacetic acidcontent of the product 3,3-dimethylbutanal is less than about 1% byweight.
 74. A process as set forth in claim 40 wherein the yield of3,3-dimethylbutanal at a turnover ratio of 5 moles 3,3-dimethylbutanalper mole catalyst active phase is at least 80% of the initial yield. 75.A process as set forth in claim 74 wherein the turnover ratio is atleast about 10 moles 3,3-dimethylbutanal per mole catalyst active phaseprior to any regeneration of the catalyst.
 76. A process as set forth inclaim 75 wherein the yield of 3,3-dimethylbutanal at a turnover ratio of10 moles 3,3-dimethylbutanal per mole catalyst active phase is at least90% of the initial yield.
 77. A process as set forth in claim 76 whereinthe turnover ratio is at least about 15 moles 3,3-dimethylbutanal permole catalyst active phase before any regeneration of the catalyst andthe yield at a turnover ratio of 15 moles 3,3-dimethylbutanal per moleactive catalyst phase is at least 95% of the initial yield.
 78. Aprocess for the preparation of 3,3-dimethylbutanol comprising: heating ahydrolysis feed mixture comprising a 3,3-dimethylbutyl ester and amineral acid in the presence of water, thereby hydrolyzing the ester andproducing a hydrolysis reaction mixture comprising 3,3-dimethylbutanol;and distilling 3,3-dimethylbutanol formed in the hydrolysis from thehydrolysis reaction mixture
 79. A process as set forth in claim 78wherein 3,3-dimethybutanol is distilled from the reaction mixture as thehydrolysis reaction proceeds.
 80. A process as set forth in claim 79wherein said hydrolysis feed mixture comprises between about 10% andabout 75% by weight H₂SO₄, between about 25% and about 95% water, andbetween about 1% and about 50% by weight 3,3-dimethylbutyl hydrogensulfate.
 81. A process as set forth in claim 80 wherein said hydrolysisfeed mixture further comprises between about 0.5% and about 50% byweight di(3,3-dimethylbutyl) sulfate, both said 3,3-dimethylbutylhydrogen sulfate and said di(3,3-dimethylbutyl) sulfate being hydrolyzedto 3,3-dimethylbutanol.
 82. A process as set forth in claim 80 whereinsaid distillation is conducted at a head pressure of between about 0.1atm and about 2 atm and a bottoms temperature of between about 35° andabout 175° C.
 83. A process as set forth in claim 82 wherein thedistillation is conducted at atmospheric head pressure and an overheadcondensate fraction rich in 3,3-dimethylbutanol is collected at atemperature of between about 90° and about 99° C.
 84. A process as setforth in claim 83 wherein said overhead condensate comprises anazeotrope of 3,3-dimethylbutanol and water.
 85. A process as set forthin claim 83 wherein said rich fraction contains at least about 50% byweight 3,3-dimethylbutanol.
 86. A process as set forth in claim 85wherein said rich fraction contains between about 75% and about 95% byweight 3,3-dimethylbutanol.
 87. A process as set forth in claim 86wherein said rich fraction condensate comprises an organic phasecontaining at least 75% by weight 3,3-dimethylbutanol and an aqueousphase comprising no more than about 2% by weight 3,3-dimethylbutanol.88. A process as set forth in claim 87 wherein 3,3-dimethylbutanolobtained in said organic phase of said rich fraction is converted to3,3-dimethylbutanal.
 89. A process as set forth in claim 88 wherein3,3-dimethylbutanol is converted to 3,3-dimethylbutanal by catalyticdehydrogenation.
 90. A process as set forth in claim 89 wherein3,3-dimethylbutanal produced in said catalytic dehydrogenation isreacted with L-α-aspartyl-L-phenylalanine 1-methyl ester in the presenceof a reducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.91. A process as set forth in claim 89 wherein the t-butylacetic acidcontent of the 3,3-dimethylbutanol product is not greater than about 1%by weight.
 92. A process for the preparation of 3,3-dimethylbutanalcomprising: contacting a gas phase comprising 3,3-dimethylbutanol and aninert gas with a dehydrogenation catalyst to produce a dehydrogenationreaction product gas containing 3,3-dimethylbutanal at a turnover ratioof at least about 5 moles 3,3-dimethylbutanol per mole catalyst activephase prior to any interruption of the reaction for regeneration of thecatalyst; and recovering 3,3-dimethylbutanal from the dehydrogenationreaction product.
 93. A process as set forth in claim 92 wherein a feedgas comprising 3,3-dimethylbutanol and an inert gas is introduced into acatalyst bed comprising a catalyst for the dehydrogenation of3,3-dimethylbutanol; and said reaction product gas is withdrawn fromsaid bed.
 94. A process as set forth in claim 93 wherein said catalystis selected from the group consisting of copper oxide, a reduced form ofcopper, silver, gold, platinum, palladium and a platinum/tin alloy. 95.A process as set forth in claim 94 wherein said catalyst comprises areduced form of copper.
 96. A process as set forth in claim 93 whereinthe dehydrogenation is conducted at a temperature of at least about 200°C.
 97. A process as set forth in claim 96 wherein said dehydrogenationis conducted at a temperature between about 200° C. and about 400° C.98. A process as set forth in claim 97 wherein the total pressure insaid catalyst bed is less than about 100 psig, and the hydrogen partialpressure is less than about 100 psig.
 99. A process as set forth inclaim 98 wherein the hydrogen partial pressure is between about 5 psigand about 20 psig.
 100. A process as set forth in claim 93 wherein saidfeed gas contains at least about 0.5% by volume 3,3-dimethylbutanol.101. A process as set forth in claim 100 wherein said feed gas containsbetween about 1% and about 25% by volume 3,3-dimethylbutanol.
 102. Aprocess as set forth in claim 100 wherein said feed gas contains betweenabout 2.5% and about 10% by volume 3,3-dimethylbutanol.
 103. A processas set forth in claim 100 wherein said gas phase flows over saidcatalyst bed at a space velocity of at least about 0.25 sec⁻¹.
 104. Aprocess as set forth in claim 103 wherein the dehydrogenation reactionis conducted at temperature of between about 200° C. and about 400° C.under a hydrogen partial pressure no greater than about 100 psig.
 105. Aprocess as set forth in claim 104 wherein volume of said catalyst bedand the surface area, activity and selectivity of said catalyst issufficient to provide a conversion of 3,3-dimethylbutanol to3,3-dimethylbutanal of at least about 50% with a residence time lessthan about 10 seconds.
 106. A process as set forth in claim 105 whereina conversion of at least about 50% is provided and maintained oversustained operations of greater than 30 days without regeneration of thecatalyst.
 107. A process as set forth in claim 106 wherein recovery of3,3-dimethylbutanal comprises cooling said dehydrogenation reactionproduct gas to condense 3,3-dimethylbutanal.
 108. A process as set forthin claim 106 wherein the condensate obtained by cooling saiddehydrogenation reaction product gas is distilled for separation of3,3-dimethylbutanal from 3,3-dimethylbutanol contained therein.
 109. Aprocess as set forth in claim 93 wherein said catalyst bed comprises afixed bed comprising a plurality of stages and is contained in areaction vessel having a chamber substantially free of catalyst betweena successive pair of said stages with respect to the passage of reactiongas through the reactor, a supply of heated gas being provided to saidchamber for reheating reaction gas entering said chamber from the stageimmediately upstream of said chamber.
 110. A process as set forth inclaim 109 wherein said reactor contains a plurality of chamberssubstantially free of catalyst, each of said chambers being locatedbetween a successive pair of said stages with respect to the directionof gas flow, a supply of heated gas being provided to each of saidplurality of chambers for reheating reaction gas entering such chamberfrom the stage immediately upstream thereof.
 111. A process as set forthin claim 92 wherein 3,3-dimethylbutanal produced in said catalyticdehydrogenation is reacted with L-α-aspartyl-L-phenylalanine 1-methylester in the presence of a reducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.112. A process as set forth in claim 92 wherein the yield of3,3-dimethylbutanol at a turnover ratio of 5 mole3,3-dimethylbutanal permole catalyst active phase is at least 80% of the initial yield.
 113. Aprocess as set forth in claim 113 wherein the turnover ratio is at leastabout 10 moles 3,3-dimethylbutanal per mole catalyst active phase priorto any regeneration of the catalyst.
 114. A process as set forth inclaim 113 wherein the yield of 3,3-dimethylbutanal at a turnover ratioof 10 moles 3,3-dimethylbutanal per mole catalyst active phase is atleast 90% of the initial yield.
 115. A process as set forth in claim 114wherein the turnover is at least about 15 moles 3,3-dimethylbutanal permole catalyst active phase before any regeneration of the catalyst andthe yield at a turnover ratio of 15 moles 3,3-dimethylbutanal per moleactive catalyst phase is at least 95% of the initial yield.
 116. Aprocess for the preparation of 3,3-dimethylbutanal comprising: preparinga slurry comprising a particulate dehydrogenation catalyst and3,3-dimethylbutanol; converting 3,3-dimethylbutanol to3,3-dimethylbutanal by catalytic dehydrogenation in said slurry, therebyproducing a dehydrogenation reaction product slurry comprising saidcatalyst and 3,3-dimethylbutanal; and recovering 3,3-dimethylbutanalfrom the dehydrogenation reaction product slurry.
 117. A process as setforth in claim 116 wherein said catalyst is selected from the groupconsisting of copper oxide, a reduced form of copper, zinc oxide,silver, gold, platinum, palladium and a platinum/tin alloy.
 118. Aprocess as set forth in claim 117 wherein said catalyst comprises areduced form of copper.
 119. A process as set forth in claim 116 wherein3,3-dimethylbutanal produced in said catalytic dehydrogenation isreacted with L-α-aspartyl-L-phenylalanine 1-methyl ester in the presenceof a reducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.120. A process for the preparation of 3,3-dimethylbutanal comprising:contacting 3,3-dimethylbutanoic acid or an ester thereof with a reducingagent, thereby producing 3,3-dimethylbutanol; and converting3,3-dimethylbutanol to 3,3-dimethylbutanal.
 121. A process as set forthin claim 120 wherein 3,3-dimethylbutanoic acid or an ester thereof iscontacted with a reducing agent selected from the group consisting of analkali metal borohydride, and lithium aluminum hydride.
 122. A processas set forth in claim 120 wherein 3,3-dimethylbutanoic acid or an esterthereof is reduced to 3,3-dimethylbutanol by catalytic hydrogenation.123. A process as set forth in claim 120 wherein 3,3-dimethylbutanoicacid is contacted with lithium aluminum hydride.
 124. A process as setforth in claim 120 wherein 3,3-dimethylbutanoic acid is contacted withsodium borohydride.
 125. A process as set forth in claim 120 wherein3,3-dimethylbutanol is contacted with an oxidizing agent for theoxidation of the alcohol to 3,3-dimethylbutanal.
 126. A process as setforth in claim 125 wherein said oxidizing agent comprises copper oxideeffective for stoichiometric oxidation of an alcohol to a correspondingaldehyde.
 127. A process as set forth in claim 120 wherein3,3-dimethylbutanol is contacted with a catalyst effective fordehydrogenation of 3,3-dimethylbutanol to 3,3-dimethylbutanal.
 128. Aprocess as set forth in claim 127 wherein said catalyst is effective forthe anaerobic dehydrogenation of 3,3-dimethylbutanol, said catalystbeing contacted with 3,3-dimethylbutanol in the substantial absence ofmolecular oxygen.
 129. A process as set forth in claim 127 wherein saidcatalyst is effective for the oxidative dehydrogenation of3,3-dimethylbutanol, said catalyst being contacted with3,3-dimethylbutanol and molecular oxygen.
 130. A process as set forth inclaim 127 wherein said catalyst comprises an active phase comprising areduced form of copper obtained in a stoichiometric redox reactionbetween copper oxide and 3,3-dimethylbutanol.
 131. A process as setforth in claim 127 wherein said catalyst comprises an active phasecomprising a reduced form of copper obtained by contacting copper oxidewith a reducing agent selected from the group consisting of molecularhydrogen, sodium borohydride, hydrazine.
 132. A process as set forth inclaim 127 wherein vapor phase 3,3-dimethylbutanol is passed over a bedcomprising a catalyst for the dehydrogenation of 3,3-dimethylbutanol to3,3-dimethylbutanal.
 133. A process as set forth in claim 132 whereinsaid catalyst is effective for the anaerobic dehydrogenation of3,3-dimethylbutanol, said vapor phase being substantially free ofmolecular oxygen.
 134. A process as set forth in claim 132 wherein saidcatalyst is effective for the oxidative dehydrogenation of3,3-dimethylbutanol, said vapor phase comprising molecular oxygen. 135.A process as set forth in claim 120 wherein isobutylene and ethylene arebrought into contact with sulfuric acid in an alkylation/esterificationreaction zone without introduction of any organic solvent into saidreaction zone from any extraneous source.
 136. A process as set forth inclaim 120 wherein said 3,3-dimethylbutanal is reacted withL-α-aspartyl-L-phenylalanine 1-methyl ester in the presence of areducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.137. A process for the preparation of 3,3-dimethylbutanal comprising:hydrolyzing a substrate selected from the group consisting of1-chloro-3,3-dimethylbutane, 1-bromo-3,3-dimethylbutane and1-iodo-3,3-dimethylbutane to produce 3,3-dimethylbutanol; and converting3,3-dimethylbutanol to 3,3-dimethylbutanal.
 138. A process as set forthin claim 137 wherein said substrate is contacted with an aqueous base ata temperature effective for the hydrolysis.
 139. A process as set forthin claim 138 wherein said substrate is contacted with a metal oxide at atemperature in excess of about 200° C.
 140. A process as set forth inclaim 139 wherein the substrate is contacted with a oxide at atemperature of between about 200° C. and about 400° C.
 141. A process asset forth in claim 137 wherein 3,3-dimethylbutanol is contacted with anoxidizing agent for the oxidation of the alcohol to 3,3-dimethylbutanal.142. A process as set forth in claim 141 wherein said oxidizing agentcomprises copper oxide effective for stoichiometric oxidation of analcohol to a corresponding aldehyde.
 143. A process as set forth inclaim 137 wherein 3,3-dimethylbutanol is contacted with a catalysteffective for dehydrogenation of 3,3-dimethylbutanol to3,3-dimethylbutanal.
 144. A process as set forth in claim 143 whereinsaid catalyst is effective for the anaerobic dehydrogenation of3,3-dimethylbutanol, said catalyst being contacted with3,3-dimethylbutanol in the substantial absence of molecular oxygen. 145.A process as set forth in claim 143 wherein said catalyst is effectivefor the oxidative dehydrogenation of 3,3-dimethylbutanol, said catalystbeing contacted with 3,3-dimethylbutanol and molecular oxygen.
 146. Aprocess as set forth in claim 143 wherein said catalyst comprises anactive phase comprising a reduced form of copper obtained in astoichiometric redox reaction between copper oxide and3,3-dimethylbutanol.
 147. A process as set forth in claim 143 whereinsaid catalyst comprises an active phase comprising a reduced form ofcopper obtained by contacting copper oxide with a reducing agentselected from the group consisting of molecular hydrogen, sodiumborohydride, hydrazine.
 148. A process as set forth in claim 143 whereinvapor phase 3,3-dimethylbutanol is passed over a bed comprising acatalyst for the dehydrogenation of 3,3-dimethylbutanol to3,3-dimethylbutanal.
 149. A process as set forth in claim 148 whereinsaid catalyst is effective for the anaerobic dehydrogenation of3,3-dimethylbutanol, said vapor phase being substantially free ofmolecular oxygen.
 150. A process as set forth in claim 148 wherein saidcatalyst is effective for the oxidative dehydrogenation of3,3-dimethylbutanol, said vapor phase comprising molecular oxygen. 151.A process as set forth in claim 137 wherein isobutylene and ethylene arebrought into contact with sulfuric acid in an alkylation/esterificationreaction zone without introduction of any organic solvent into saidreaction zone from any extraneous source.
 152. A process as set forth inclaim 137 wherein said 3,3-dimethylbutanal is reacted withL-α-aspartyl-L-phenylalanine 1-methyl ester in the presence of areducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.153. A process for the preparation of 3,3-dimethylbutanal comprising:preparing 3,3-dimethylbutanol, the preparation of 3,3-dimethylbutanolcomprising hydrolysis of 1-halo-3,3-dimethylbutane or1-acyloxy-3,3-dimethylbutane in the presence of a base; and converting3,3-dimethylbutanol to 3,3-dimethylbutanal.
 154. A process as set forthin claim 153 wherein preparation of 3,3-dimethylbutanol compriseshydrolysis of 1-halo-3,3-dimethylbutane.
 155. A process as set forth inclaim 153 wherein the preparation of 3,3-dimethylbutanol comprises:reaction of said 1-halo-3,3-dimethylbutane with a salt of an organicacid, thereby producing an ester of 3,3-dimethylbutanol; and hydrolyzingsaid ester in the presence of base to produce 3,3-dimethylbutanol. 156.A process as set forth in claim 153 wherein said 3,3-dimethylbutanal isreacted with L-α-aspartyl-L-phenylalanine 1-methyl ester in the presenceof a reducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.157. A process for the preparation of 3,3-dimethylbutanal comprising:reducing 1,2-epoxy-3,3-dimethylbutane oxide to 3,3-dimethylbutanol; andconverting 3,3-dimethylbutanol to 3,3-dimethylbutanal.
 158. A process asset forth in claim 157 wherein said 1,2-epoxy-3,3-dimethylbutane isreduced to 3,3-dimethylbutanol by catalytic hydrogenation.
 159. Aprocess as set forth in claim 157 wherein said 3,3-dimethylbutanal isreacted with L-α-aspartyl-L-phenylalanine 1-methyl ester in the presenceof a reducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.160. A process for the preparation of 3,3-dimethylbutanal comprising:reacting a t-butyl organometallic compound with ethylene oxide to form3,3-dimethylbutanol; and converting 3,3-dimethylbutanol to3,3-dimethylbutanal.
 161. A process as set forth in claim 160 whereinsaid organometallic compound is selected from the group consisting ofR-G and R-Li wherein R is t-butyl and G is selected from the groupconsisting of MgCl and MgBr.
 162. A process as set forth in claim 160wherein said 3,3-dimethylbutanal is reacted withL-α-aspartyl-L-phenylalanine 1-methyl ester in the presence of areducing agent to produceN-[N-(3,3-dimethybutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester.163. A process for the preparation of 3,3-dimethylbutanal comprisingcontacting 3,3-dimethylbutanol with a catalyst for the dehydrogenationof an alcohol to a corresponding aldehyde, said catalyst beingsubstantially non-toxic to humans.
 164. A process as set forth in claim163 wherein said catalyst is substantially free of chromium.